Bio 182: Chapter 12, 13 and 14

how does a cell know when to divide

#1) activation by an internal or external signal #2) inhibition by an internal or external signal - cell will halt/arrest division

M (mitosis) phase checkpoint (2 checkpoints)

(METAPHASE--> ANAPHASE) chromosomes have attached to spindle apparatus, chromosomes have properly segregated and MPF is absent -during division - sister chromatids split when kinetochores attached to the spindle - without this, some cells would get more chromosomes and others would get less (ANAPHASE--> TELOPHASE) - helps cells leave M--> G1 phase by degrading the MPFs cyclins and tumor activity - when chromosomes are separate, these cyclin-degrading enzymes are activated - without them, the MPF activity would prevent entering into cytokinesis - if cells are stop by either, they will stay in M Phase

lipid-insoluble signal molecule processing

- outside the P.M - they don't directly participate in intracellular activities, like gene expression

specialized/differentiated cells

- some cells don't divide, they do work or protect us; they die and are replaces

signal transduction with enzyme-linked receptors

- they directly catalyze a reaction in a cell - use RTK as their P.M receptors

GAP proteins

-act as transcription factors -activate pair-rule genes whose products divide embryo into smaller regions two segments wide -anterior and posterior regions - protein that deactivates and created GDP with the g-proteins - CAMP activates PKA and phosphorylates proteins in the cytoplasm - those proteins can then be transcription factors

Steps of G Protein-Coupled Receptors

1) Signal molecule arrives and binds to the transmembrane protein receptor with intracellular side couples with a useful GDP 2) receptors changes shape and activates G-protein and kicks off GDP adding a GTP - the GTP changes the g-protein shape/activity and it splits off 3) active protein interacts with plasma membrane embedded enzyme which catalyzes rah secondary messenger

Steps of enzyme linked receptors

1) a hormones binds to 2 subunits of RTK and they form a dimer 2) this RTK conformations change sets off catalytic activity and the RTK phosphorylates itself at tyrosine residues with ATP in the cell 3) proteins bind to the phosphorylated RTK forming a bridge between the receptors and a peripheral membrane protein 4) Ras; a single g-protein exchanges GDP for a GTP 4) Ras is activated and it triggers the phosphorylation and activation of the protein kinase 5) the kinase, activated by Ras, catalyzes the phosphorylation of a second kinase and then a third etc

how do cells replication

1) copying DNA through DNA replication 2) segregating the copies 3) dividing the cytoplasm to create 2 complete cells

Interphase

Cell grows, performs its normal functions, and prepares for division; consists of G1, S, and G2 phases - the resting phase between successive mitotic divisions of a cell, or between the first and second divisions of meiosis. - the rest of the time; no dramatic changes - the chrosomes uncoil into long-thin structures and no longer appear as individual threads - cells spend the most time here - cell is growing and preparing to divide into a multicellular individual - replicates in S phase and then condenses

PKA

2 catalytic and 2 regulatory subunits - camp binds to the regulatory subunits and alters its confirmation and press he now active catalytic subunits - PKA phosphorylates other proteins and transcription factors - a molecule with 4 SUBUNITS

eukaryotes have

46 chromosomes in each somatic cell nucleus - during interphase--> they are replicated - 46 chromosomes with 2 sister chromatids - connected at centromere

G protein

A GTP-binding protein that relays signals from a plasma membrane signal receptor, known as a G protein-coupled receptor, to other signal transduction proteins inside the cell. - protein alive with GTP and inactive with GDP

Steps of G protein activation

1) ligands binds to G-protein receptors with conformational change 2) activated the G-protein 3) G-prtoein has 2 subunits that dissociate (alpha, beta, and gamma) 4) the affinity for GDP is lowered 5) GDP to GTP 6( subunits dissociated 4) gamma and alpha + beta (2 molecules form)

signal transduction and kinase activity

1) receptor activate a conformation change in receptor mediated by ligand changes the functional capacity of the receptor - activation 2) signal transduction: initial signal is transacted to a new signal in the cell 3) cellular response 4) in activation the response in the absence of the stimulus

cadherin

A calcium-dependent adherence protein, important in the adhesion of cells to other cells. - at adhering functions - after translated from mRNA, the cadherin protein is transported to the P.M - establishes itself as a transmembrane protein - has distinct cytoplasmic and extracellular domains - the extracellular domain is where adjacent cells with cadherins of similar type link together - there are 5 domains that interact with each other in a calcium dependent matter - +Ca+--> they form dimers - one cell has cis-dimers and other other has transducer - Ca+--> removals= cadherin fail to bind - the cytoplasmic region forms with catering molecules likes the transmembrane cadherin protein with the actin cytoskeleton

Cyclin

A cellular protein that occurs in a cyclically fluctuating concentration and that plays an important role in regulating the cell cycle. - the second MPK subunits protein - their concentrations fluctuate throughout the cell cycle - peaks during M phase and builds up doing interphase - MPK is only active with cyclin bound to the protein kinase subunits - regulated the formation of the MPF dimer, since the kinases are always present

M phase-promoting factor (MPF)

A complex of a cyclin and cyclin-dependent kinase that, when activated, phosphorylates a number of specific proteins needed to initiate mitosis in eukaryotic cells. - factor in M-phase cells that initiates M-phase in other arrested cells - contains a protein kinase and a cyclin - 2 distinct protein kinase and a cyclin - polypeptide units

Proteasomes

A giant protein complex that recognizes and destroys proteins tagged for elimination by the small protein ubiquitin.

tumor

A mass of abnormal cells that develops when cancerous cells divide and grow uncontrollably. - cells that are effective and keep dividing; disregarding cell cycle checkpoints and creating a mass of cells - interactions around regulatory proteins at each checkpoint decide whether a cell will proceed with division or not

Ubiquitin

A protein that attaches itself to faulty or misfolded proteins and thus targets them for destruction by proteasomes - destructs MPF

G-protein coupled receptors

A signal receptor protein in the plasma membrane that responds to the binding of a signaling molecule by activating a G protein. Also called a G protein-linked receptor. - initiate the production of intracellular secondary messengers - amplify signal - g-proteins span P.M anchor and are closely associated to certain signal receptors - activated by signal receptors that trigger second messenger creations

cross talk

A type of interference caused by signals traveling on nearby wire pairs infringing on another pair's signal. - synthesizing input from many signals - cells receive the process many signals at a time - complexity and crossing paths allows for a cell to respond to many different signals in an integrated way - multiple signal interactions that modify the cell response 1) a pathway can inhibit another pathway even with the appropriate signal present 2) one can stimulate another pathway leading to two responses for one signal 3) there are multiple steps in each pathway to allow for regulation and comprehension of many signals at a time

first messenger

A water soluble hormone that binds to its receptor at the outer surface of the plasma membrane. - the signaling molecule that arrived to the cell surface

Subunits of G protein

Alpha, beta, gamma Inactive form: alpha binds GDP and is in complex with B and G Ligand binding --> GDP replaced with GTP --> alpha dissociates --> activates or inhibits adenylate cyclase GTP dephosphorylated to GDP --> alpha rejoins G protein complex - the alpha and gamma subunits have a lipid tail to bind to the plasma membrane - no ligand= GDP - signal ligand= GTP - sometimes the g-protein will always be bound to the receptor, and something it only ends when there's a signal - the receptor causes a conformation change in the alpha subunits that causes it to release the GDP and take in GTP - the activated alpha GTP subunit can either stay with the beta/alpha subunits or dissociate

adenylyl cyclase

An enzyme that converts ATP to cyclic AMP in response to an extracellular signal. - with ATP, produces cAMP in the plasma membrane - a membrane bound enzyme that has a catalytic domain that is activated by the GTP form of the g-protein form (alpha subunit) - converts ATP to CAMP--> acts as a 2nd messenger that relays the signal

protein kinase

An enzyme that transfers phosphate groups from ATP to a protein, thus phosphorylating the protein. - activated by 2nd messengers; enzymes that activate/inactivate other proteins by adding a phosphate group

Mitogen-activated protein kinase (MAPK)

Any of a class of enzymes involved in signal transduction pathways that often activate cell division. In a cell, different types of MAPKs are organized in a series, where one activates another via phosphorylation. - the numbered kinases that are amplified because there are more activated enzymes as each stage professes - mito- mitosis

Cytokenesis in animal cells

Two new daughter cells are formed - division of the cytoplasm

control of the cell cycle

Cell-cycle length can vary greatly among cell types Variation in the length of G1 phase is responsible for differences G1 phase is essentially eliminated in rapidly dividing cells Nondividing cells get permanently stuck in G1 phase This arrested stage is called the G0 state The rate of cell division can also respond to changes in environmental conditions These variations in cell-cycle length suggest The cell cycle is regulated Regulation varies among cells and organisms - the cell cycle is different between different types of cells - intestinal cels divide and replace tissue daily - nerve/muscle cells never divide once they mature

G1 checkpoint

Checks the surroundings to make sure the conditions are favorable and the cell is healthy enough to enter the next stage - either divide or enter G0 factors: cell size (must be a certain size for daughter cells to function, well) and nutrients availability (arrest at G1 without it)

Horomones

Chemicals produced by your glands that regulate the activities of different body cells - info-carrying molecules secreted by plant and animal cells into bodily fluids and act on distant target cells - small molecules with peptides, steroids, gases etc.

Neurotransmitters

Chemicals that transmit information from one neuron to another - a signaling molecule that keeps distant cells in touch by opening or closing ion Chanels in the plasma membrane in distance cells - changes electrical properties of the P.M

camp

Cyclic adenosine monophosphate, a ring-shaped molecule made from ATP that is a common intracellular signaling molecule (second messenger) in eukaryotic cells. It is also a regulator of some bacterial operons. - secondary messenger - cyclic AMP - ATP + AC--> cAMP (activation) - this cyclic AMP activates inactive phosphorylase kinases (PKA) - the cycle of phosphorylation continues - the PKAs can activate a transcription factor (inactive) in the nucleus to express an activated target gene - this is a POST-TRANSLATIONAL modification (phosphorylation) - activates camp-dependent (PKA)

Stages of the cell cycle

G1, S, G2, M - G1= gap (growth) - S= DNA replication - G2= gap (cell synthesis proteins for chromosome sorting and division) - theses are all interphase - Mitosis= division

GEF vs GAP

GEF adds GTP to Ras GAP takes off ras to GDP - this is not a phosphorylation; they just switch GTP to GDP or GDP to GTP - both GTPases

Ras

GTPase protein that binds to GTP or GDP

endocrine system

Glands secrete hormones that regulate processes such as growth, reproduction, and nutrient use (metabolism) by body cells. - travel through the bloodstream to far target cells with glands; hormones - this is how we normally think of cell-cell communication and all its complexity - long-distance

GEF

Guanine nucleotide exchange factors, that causes a protein to lose a GDP and replace it with a GTP - activated by the g-protein receptor - activates the g-protein by switching the GDP to a new GTP - alpha-GDP--> alpha-GTP

sister chromatids

Identical copies of a chromosome; full sets of these are created during the S subphase of interphase. - chromatid copies that remain attached at their centromere - each chromosomes has 2 chromatids, but its still considered a single chromosomes

kineticore microtubules

Kinetochore microtubules attach the chromosomes to the spindle pole; interpolar microtubules extend from the spindle pole across the equator, almost to the opposite spindle pole; and astral microtubules extend from the spindle pole to the cell membrane.

Cells alternate between

M phase and interphase - division and non-division

ras activates

MAP kinase pathway - kinase cascade

secondary messenger

Molecules that relay signals from receptors on the cell surface to target molecules inside the cell, in the cytoplasm or nucleus. Essential for hormones that cannot cross the plasma membrane - small molecules that convey the message from the receptor to the inside of the cell

NLS

Nuclear localization signal specific amino acid sequences that are recognized by transport receptors and direct the transport of proteins from the cytoplasm through the nuclear pore complex into the nucleus.

gap junctions

Points that provide cytoplasmic channels from one cell to another with special membrane proteins. Also called communicating junctions. - acts as a channel between cells so adjacent cells can communication

tumor supressor proteins

Repair damaged DNA Control cell adhesion Inhibit the cell cycle in the cell-signaling pathway - regulatory proteins, like P53,

M checkpoint

Spindle assembly checkpoint. Mitosis will not continue if chromosomes are not properly aligned. - metaphase meet chromosomes align in a timely way - are the spindles intact and chromosomes at the right alignment

How do distant cells communicate?

The activities of cells, tissues, and organs in different parts of a multicellular organism are coordinated by long-distance signals

G1 phase

The first gap, or growth phase, of the cell cycle, consisting of the portion of interphase before DNA synthesis begins. - gap between the end of M and star of S - allows the cell to grow and replicate organelles, son it will be able to divide into 2 cells; that can functional formally - cells perform their functional roles mostly during G1 phase, and this is where the cell decides to begin replication, and transitions to S-phase occurs

signal transduction

The linkage of a mechanical, chemical, or electromagnetic stimulus to a specific cellular response. - made by the signal arriving at the surface of the cell and produces an intracellular signal or "signal transduction pathway," - conversion of a signal from one form to another - extracellular signal to an intracellular signal

M phase

The phase of the cell cycle that includes mitosis and cytokinesis. - separates their chromosomes - condenses into compact structures during M phase

difference between polar microtubules and kineticore microtubules

The polar microtubules overlap near the equatorial plane of the spindle. The kinetochore microtubules attach to the kinetochore of chromosomes. The kinetochore of a chromosme is formed at the centromere by the assembly of several proteins and is partly responsible for chromosome movement.

cell cycle

The regular sequence of growth and division that cells undergo - orderly sequence of events that leads to eukaryotic cell through the duplication of its chromosomes to the time it divides

G2 phase

The second gap, or growth phase, of the cell cycle, consisting of the portion of interphase after DNA synthesis occurs. - gap between end of S and start of M - the G2 phase prepares for the M phase

S phase

The synthesis phase of the cell cycle; the portion of interphase during which DNA is replicated. - when the chromosomes are replicated - scientists added radioactive phosphorus to cels, and the cells synthesized DNA would incorporate the phosphate into their nucleotides - active DNA synthesis was in some interphase cells and other in M-phase cells - S-phase in a part of interphase that copies/replicate DNA and is physically separated from the M-phase, where the partitioning of replicate chromosomes occurs

Phosphorylation

The transfer of a phosphate group, usually from ATP, to a molecule. Nearly all cellular work depends on ATP energizing other molecules by phosphorylation. - adding phosphate group, and its the primary mechanisms for information change

p53

This tumor suppressor gene causes cell cycle arrest in G1, providing time for DNA repair. If repair is successful, cells re-enter the cycle. If unsuccessful, apoptosis - tumor supressor protein - a gene in DNA that prevents cancer - also a T.F that regulates other gene involved in cell cycle - cancer (1/2) patients have mutation in p53 3 roles: - halts cell cycle (inhibition) - DNA repair (stops cells to repair) - if the damage is too great, aptosis

cell-cell signaling

molecular signals from one cell are received by a neighboring cell, setting up signal transduction pathways that change gene expression - signal transduction is the process whereby one type of signal is converted to a another

phosphorylation cascade

a sequence of events where one enzyme phosphorylates another, causing a chain reaction leading to the phosphorylation of thousands of proteins - sequence of protein modifications in a cell initiated by mitogens

what is a chromosome

a threadlike structure of nucleic acids and protein found in the nucleus of most living cells, carrying genetic information in the form of genes. - threadlike structure with a single long DNA double helix wrapped around Huston proteins in a highly organized manner

Myc

a transcription factor that is required to activate genes necessary for G1 to S-phase transition

Gene

a unit of heredity that is transferred from a parent to offspring and is held to determine some characteristic of the offspring. - a region of DNA on the chrome that codes for a protein or RNA - before mitosis, each chromosome is replicated - the chromosomes condense into compact structures; before mitosis and move around the cell efficiently -then a copy of each chromes Is distributed to each other th two daughter cells

GTP + G-protein

activated

ras + GTP

active

MAPs

acts as Kinase (+Pi) and activate transcription factors - one is Myc (in cell division)

Aneploidy

addition or deletion of a chromosome - abnormal number of chromosomes

gap phases

allow the cell to grow large enough and synthesize enough organelles to ensure the daughter cells will be normal in size and function - G1 and G2 - a gap in interphase when DNA is not replicated - between the end of s-phase and beginning of M - chromosomes replication is complete, but beginning of mitosis hasn't begun - another gap between the end of M-phase and start of S phase

G0 arrest

arrested state in nondividng cells that enter once they mature - the cells' division can be effected by the environment, too - if a cell is damaged or part of an organism is hurt, cells will divide until it heals - in unicellular eukaryotes, they only divide if the environment is rich in nutrients, elsewise, they enter G0 - yeast, protist, etc

G2 checkpoint

asses if DNA replication has occured, go ahead signal triggers mitosis - after S phase, at the boundary between G2 and M - MPF is the key signal triggering its onset, and if DNA is damaged or chromes not correctly replicated, the inhibitory Pi on CDK stays - also cells respond to signals from other cells or internal signals about size

difference cyclins control parts of cell cycle

more cyclins through the process than MPF cyclins - G1-S phase cyclin - S-G2 cyclin - G2- M cyclin - they come in, help the cell move from phase to phase and then go on; degrade

intracellular receptors

receptors located inside the cell rather than on its cell membrane - inside the cell - hydrophobic, lipid-soluble ligand - receptors has conformational change and enters the nucleus - to turn on/off genes as a T.F

Cdk inhibitors

regulate activity of cyclin-CDK complexes; 'tumor suppressors' - CDKI - activated by p53

GTP

regulates G-protein activity (guanosine triphosphate) - G-proteins bind to GTP or GDP - the negative charge alters protein/shape/activity - the more potential energy, the closer the 3 phosphate groups are

cell surface receptors

bind specific molecules that are called ligands. Ligands are molecules that bind to macromolecules (e.g., binding to a receptor). An example of a ligand is a neurotransmitter released from a nerve cell that binds to the cell surface receptor of a muscle cell to initiate contraction - g-protein receptor with ligand outside the cell - binds to the GTP= active - with ligand on receptor, the alpha binds to GTP - then AC created CAMP with ATP - creates a secondary messenger

ion channel receptors

binding of ligand causes conformational change when gate opens specific ions can pass through - signal transduction opens these ion channel receptors allowing for ions to diffuse through

binding proteins

binds G-protein to the RTK

hormone/steroid acceptors

binds to hormone and is activated - the protein receptor is activated, and the NLS is exposed - many diseases can be viewed as effect in signaling; or signal transduction/protein receptors

ligand dependent activation

they activate the receptor, therefor the process without the ligand

G1/S phase cyclins

genes required for S phase (DNA replication) to be replicated - dependent of growth factors outside the cell tells the M

internal signals

chromosomes not aligned send molecule signal that delays mitosis

2 classes of CDKI

class 1 - G1 CDK1 - cell arrests in G1 - messed with CDK's active sites class 2 - G2/S Phase CDK1 - uses ATP as a substrate to add phosphate - binds with the ATP region of CDK - CDK is messed up - cyclin can bind with CDK, but the phosphorylation of downstream proteins don't work - cell is arrested there

external signal

growth factors, proteins released by certain cells that stimulate other cells to divide - growth factors; proteins released by certain cells that stimulate other cells to divide (paracrine system)

compared to cytoplasmic receptors, transmembrane receptors?

can have more responses inside the cell

Mitosis

cell division in which the nucleus divides into nuclei containing the same number of chromosomes - division of the nucleus

signalling process

cell receives signal on receptor and must process it

signal response

change in gene expression or existing protein activity in a cell

secondary messengers

conveys message of neurotransmitter from cell membrane to internal cell, regulate metabolism and development - non-protein signaling molecule that has an intracellular response to the 1st messenger - g-proteins liken the extra and intracellular signals - easily diffuse across cell - produced quickly in large quantities - a single messenger can have many roles in the same cell or different cells types receiving the same signaling molecules - sometimes, it requires many 2nd messengers to respond to a signaling molecule

advantages of 2nd messenger

many steps of regulation, amplification; many targets

cell cycle regulatory molecules

found out by fusing cells during different stages of their cell cycles and went hey fused; creating 1 cell with 2 nuclei, a nucleus changes phase

differences between cell cycles in different types of cells

depend on length of G1 phase - rapidly-dividing cells have a very short G1 phase

how to stop responses through turning off intracellular signals

dephospho rylation: phophsatases romove Pi from protein with phosphate - kinases added - hydrolysis of GTP with G-proteins: add or take off Pi to prepare GTP/GDP - gap catalyzes GDP with ras= inactive

when a ligand binds

dimerization and autophosphorylation occur - receptors are phosphorylated - RTK is dimerized

mitosis + cytokinesis

division of a cell into two identical daughter cells that are themselves either new organisms or additional cells of a multicellular organism - genetically identical with amp number of chrosomes daughter cell

cytokinesis

division of the cytoplasm to form two separate daughter cells - division of the cytoplasm - microfilaments (actin) ring associated with plasma membrane - myosin miter protein causes actin ring and plasma membrane pinches - at location of old metaphase plate

How is MPF turned off?

enzyme complex is activated during anaphase which degrades cyclin - during anaphase, an enzyme degraded the MPF's cyclin #1) negative feedback--> process is slowed down by a product of the process - MPK is turned off by an enzyme complex activated in mitosis #2) destruction of proteins--> anaphase activated enzyme complex adds small proteins called ubiquitous to KPF's cyclin subunit - they make the subunit for destruction by protein complex proteasome

protein kinase on MPF

enzyme that catalyzes the transfer of a phosphate group from an ATP to a target protein - phosphorylates proteins that trigger an ones in the m-phase in cells - they are ALWAYS present throughout cell cycles, so they need cyclins to be active

phosphodiesterase

enzyme that degrades cAMP, producing AMP, to terminate signaling - deactivated CAMP (activation) to AMP (non-active)

cyclin-dependent kinase

enzyme to which cyclin binds during interphase and mitosis, triggering and controlling activities during the cell cycle - protein kinase subunit of MPK - MPK is a dimer with cyclin and cyclin-dependent kinase - the cyclin subunit regulates the formation of the MPF dimer

Polar Mictrotubule

extend from spindle pole at the centrosome; overlap in the center - the centrosomes move to the opposite poles

Prophase

first and longest phase of mitosis in which the genetic material inside the nucleus condenses and the chromosomes become visible - during interphase, the chromosomes are uncondensed; so the chromosomes need to condense to move around the cell - the spindle apparatus forms - moves chromosomes and separates sister chromosomes (late mitosis) - cytoskeleton material: microtubules - the microtubules move chromatids - (- end)= centrosome (MTOC) and (+ end)= to chromatid

receptors can be blocked

for example, beta-blockers bin to adrenaline receptors. when it binds to receptors in heart cells, it stimulates rapid and forceful contractions. if a physician wants to reduce heart cell contractions to reduce blood pressure, they'd prescribe a beta-locker. - certain drugs, like beta-blockers, bind to receptors t inhibit a hormone or small molecule's effects

Scaffold proteins

improve the efficiency of a signaling cascade by holding all the participating enzymes in close proximity - holds proteins in cascade close to the speed by it lowers amplification y limiting the number of proteins phosphorylated

When is the MPF concentration the highest?

in mitosis and G2 boundary to activate mitosis - drops in concentration after mitosis due to protein degradation

Social signals received by a cell during its G1 checkpoint could tell the cell...

in multicellular organisms, they require signaling molecules from other cells

GTP--> GDP + Pi + protein

inactivated and needs a new GTP replacement

GDP + G-protein

inactive

ras + GDP

inactive

phosphorylation is the primary mechanisms for

information transfer - kinase transfer's phosphate of ATP--> OH- on a proteins

lipid-soluble signal molecule processing

inside the plasma membrane and cell - hydrophobic - steroid hormones are hydrophobic - estrogen and cortisol - they are carried through the bloodstream by hydrophilic proteins to get to their target cell - they need carrier proteins - a hormone-receptor complex is formed - carried to the nucleus to trigger changes to gene expression - the expression of a gene effected -> a new protein that alters cell

Steps of Mitosis

interphase, prophase, metaphase, anaphase, telophase, cytokinesis - 1) during interphase, the chromosomes are uncondensed; what processes occur - chromatid decondensing - DNA replication and gene expression occur, and they require unwound chromosomes so that the DNA replication or transcription machinery can associate with DNA to synthesis complementary DNA or mRNA

where does this interaction between signal molecule and transmitter take place

it depends on the signal molecule's ability to pass through the plasma membrane - most lipid soluble singling molecules can diffuse across the polar regions on the plasma membrane - their receptors are inside - large/hydrophilic signaling molecules are lipid insoluble - their receptors are on the surface

if you have no signal to transmit and mitogen-activated protein kinases (MAPKS) are activated

it tells the cells to divid and it keeps on dividing forever - defective RAS (always on) - the MAPKS would tell the cells to keep on diving forever - this is a type of cancer

what would happen to g-protein if GEF was mutated?

it would remain "off" (GDP bound)

ras' activity is determined by GTP/GDP bound to it

job of GEF or GAP - ras GTPases= GEF/GAP - many mutations in activation proteins can cause cancer - if the RAS is always on, it activated MAPKs and then Myc (transcription factors)

phosphorylation

kinase

Wee I

kinase protein that adds 2 Pi - inhibitory and activating

factors of division

kinases (add Pi) - phosphatase (removes Pi) - protein degradation - signaling pathway

inside receptors

most lipid-solouble signaling molecules can diffuse across the hydrophobic region of the membrane and enter the cytosol of their target cells, the receptors inside the cells. - hydrophobic single ligand - carried by hydrophilic carrier proteins to P.M - pass through the P.M and causes a conformational change in receptor protein - T.F in nucleus

epithilial cells

multiple tissues or epethial cells can process a signal, though -identical receptors in diverse cells

Pro-metaphase

nuclear envelope breaks down, the centrioles move to opposite side of the cell microtubules(spindle fibers) form and attach to chromosomes at the centromere(on the kinetochore disk)spindle fibers start aligning the chromosomes - nuclear envelop disintegrate s - Kinetic-ore microtubules originate in the MTOC and attach to chromosomes at the kinetochore which are assembled at the MTOC

chromatid

one of two identical "sister" parts of a duplicated chromosome - a double-stranded DNA copy in a replicated chrosomes - before mitosis, the 2 chromatids are joined by cohesion - during mitosis, these connected are removed except at the centromere

how to stop this pathway

phosphodiesterase (PDE) inactivate CAMP--> AMP - dephospho rylation of PKE - hydrolysis of GTP on g-proteins (active) - GAP protein (GTP-ase) - remove Pi--> GDP - cells can respond to signal mechanically, transcriptionally and metabolically

How is MPF turned on

phosphyation of one of its site activates the kinase, phosphorylation of the second inhibts the kinase. both are phosphorylated after cyclin binds to Cdk. That allows the dimer concentration to increase without prematurely starting the M phase. in late G2 phase, an enzyme removes the inhibiting phosphate. - the activity of the MPFs CDK subunit is further regulated by 2 phosphorylation sites - 1 site activates and another inhibits - this occurs after the cyclin binds allowing for dimer concentration to increase but not trigger M phase prematurely in the cell - in late G2--> enzyme removes Pi on active site of CDK that inhibits - dephospho-rylation of inhibitor Pi and addition of activating Pi - the chromosomes condense and spindle apparatus forms

G-protien coupled receptors

plasma membrane receptors that are associated with G proteins act as "on/off switches) GTPase enzyme (if lacks GTPase receptor the cell will remain constantly active) proteins - 7 membrane-spanning regions - activation stimulates change in g-protein - an active enzyme will catalyze a secondary messenger

Apoptosis

programmed cell death

dephosphorylation

protein phosphatases remove the phosphates from proteins

signal receptors

proteins that change their shape or activity after binding to a signaling molecule - protein that changes its shape and activity after binding to a signaling molecules - this shape change is how a signal is passed from signaling molecule to the receptor - only the correct signal accepter can revise and process the signal molecules message - they have to have the correct receptor

RTK

receptor tyrosin kinases example of enzyme linked receptors composed of a monomer that dimeizes upon ligand binding dimer is active form that phosphates additional cellular enzymes - including itself - they are receptor tyrosine kinase; an enzyme-linked receptor

no ligand

receptors aren't dimerized

phosphotase

removes a phosphate group from a molecule - rave phosphate groups from components of the phosphorylation cascade, causing the response to stop - happens if stimulation of RTK ends at the beginning - 2nd messengers are very short lived in cytosol - if you have no signal to transmit and mitogen-activated protein kinases (MAPKS) are activated; it tells the cells to divid and it keeps on dividing forever

phosphatase

removes phosphate - removed inhibitory phosphate from MPK to activate it to take it from G2--> M; only goes when the chromosomes/DNA replicated etc. - they can either be activators or inhibitors

which proteins are targets for T.F to turn on S phase

replication proteins - helices, DNA polyermases, topoisomerase, ligase, SSBPs

Why cells divide

reproduce organism, reproduce dead or dying cells, to produce gametes. - reproduction - gametes (meiosis) - egg and sperm creation through gamut division - growth and development - to mature - tissue renewal - we all start out as one cell: gamate; fixes damaged cells

Metaphase

second phase of mitosis, during which the chromosomes line up across the center of the cell - chromosomes line at the metaphase plate - the spindle apparatus is complete - metaphase plate

paracrine signaling

secreted molecules diffuse locally and trigger a response in neighboring cells - released by cells into the extracellular fluid; act locally

autocrine signaling

secreted molecules diffuse locally and trigger a response in the cells that secrete them - the target cell is also the secreting cell; cells own receptors are stimulated yb the cell's own signals; important in development - cell secretes signaling molecules that can bind back to its own receptor

intracellular signals amplified and diversified

signal amplification - hormones signal is amplified as it changes form - makes it possible for hormones to effect many different molecules in the cell - takes place at the plasma membrane resulting in a secondary signal involving many ions or molecules

how could you have a mutation in Ras that leads to increased signaling and cancer?

slow down hydrolysis of GTP by Ras - GTP--> GDP slows down, so the Ras + GTP is present more and activated longer - GEF and GAP don't phosphorylate, they just switch

signal reception

special protein receptors in the cell membrane bind to signaling molecules outside the cell. - hormones and other cell-cell signaling molecules deliver their message by binding to receptor molecules - changes shape/confirmation of the receptor

get adds

the GTP to the rams - ras is downstream target of the tyrosine receptor (RTK)

many signaling pathways elicit multiple different effector responses; which are possible mechanisms by which ligands bonding to one RTK can lead to many responses inside the cell?

the RTK could activate adapter proteins (GEF) - the kinases phosphorylate different transcription factors - new transcription factors activated by the pathway activate new genes

consequence of a cell that processes a mutation that inhibits the production of steroid receptors?

the cell will divide less, since steroids (ligands) with cell division stops

what would happen if a kinetochore microtubule did not attach to the kinetochore of a sister chromatid

the chromosome doing anaphase, the cell would have one fewer chromosome and a cell with one more chromosome than normal

Telophase

the final phase of cell division, between anaphase and interphase, in which the chromatids or chromosomes move to opposite ends of the cell and two nuclei are formed. - nuclear envelope reforms around each set of chromosomes - the chromosomes start to decondense - since elongated cell with 2 nucleuses

GEF

the link or adaptor protein between the tyrosine receptor protein (RTK) and the ras protein that either has GTP or GDP

receptors are dynamic

the number of receptors in a particular cell may decline if the hormonal stimulation occurs at high levels over a long time. the abilityy of a receptor to bind tightl to a signaling molecule may also decline in reponse to intensive stimulation. as a result, sensitivity to a particular hormone may change overtime. - the more hormonal stimulations, the less receptors and the less ability there is for it to bind tightly to a receptor - there is a sensitivity to a certain hormone for a cell changes overtime

damage to DNA

the protein p53 activates genes that stop the cell cycle until damage can be repaired or causes apoptosis: cell's programmed controlled destruction

Centromere

the region of the chromosome that holds the two sister chromatids together during mitosis - a specialized region of the chromosomes with a connection between chromatids

Anaphase

the stage of meiotic or mitotic cell division in which the chromosomes move away from one another to opposite poles of the spindle. - sister chromatids split - chromosomes move towards opposite poles of cell (kinetochore microtubules) - poles of cell pushed farther apart with polar microtubules - cohesion proteins that hold the chromosomes split - they form independent chromosomes that move towards the poles of the cell due to the shortening of the kinetochore microtubules - motor proteins on the polar microtubules help move the poles apart

signaling pathways activated by G-protein-linked receptor and receptor tyrosine kinase are sometimes connected

they can talk to each other to influence the expression of a gene - cross-talk - 2nd messengers are amplified to activate many proteins - exp: Pka activates many protein transcription factors - cell types can respond to signal ligands in different ways

PDGF

type of ligand attaching to receptor and stimulates division near wounds to repair damaged cells - platlette derivative G.F

signal deactivation

• Turning off cell signals is just as important as turning them on. • Cells have automatic and rapid mechanisms for signal deactivation. - These mechanisms allow the cell to remain sensitive to small changes in the concentration of hormones or in the number and activity of signal receptors. 0 they have built in

Mitogens

•Stimulate cell division by overcoming the braking mechanisms that block the progression through the cell division cycle - signaling molecules that activate cell division