quiz 3

If protein synthesis inhibitors are added along with growth factors to quiescent cells

only early response genes are induced and delayed genes are blocked

Synthesis of second messengers DAG and IP3 from phosphatidylinositol (PI)

α1 adrenergic

Switching mechanism of G proteins

γ-phosphate of GTP interacts with backbone amide groups of a conserved threonine and glycine residue

G-protein coupled signaling always has what 3 components? (choose 3)-methylation of G-protein-receptor tyrosine kinase-nuclear receptor-an effector enzyme in the plasma membrane-7TM receptor-internalization of the receptor-G-protein

-an effector enzyme in the plasma membrane -7TM receptor -G-protein

A signal transduction pathway involving a G protein, a second messenger, a protein kinase, and several target proteins

1) Binding causes conformation change 2) Activation of G-protein (GTPase) exchange GDP!GTP 3) Activated G-protein bind and activates enzyme that synthesizes a second messenger 4) Second messenger binds & activates kinase 5) Kinase phosphorylates targets 6) Targets do activity

Phosphoinositide coupled GPCR

3-4. IP3 gated Calcium channels in ER membrane open and release Calcium 5. Recruitment of Protein Kinase C to the plasma membrane 6. DAG, associates with PKC for its activation

Recruitment of ______________ causes internalization

ARRESTINS

29. The following kinases are activated by DNA damage; a. cdk4-cyclinD and cdk1-cyclinB b. ATM and Chk2 c. DNA PK and Ku70 d. ATM and cdk1-cyclinB

ATM and Chk2

The following kinases are activated by DNA damage;

ATM and Chk2

the neurotransmitter at the neuromuscular junction between the motor nerve and skeletal muscle

Acetylcholine

Gated ion Channels

Ach receptor

32. Which cyclin increases during G2 to prepare for mitosis? 1. A 2. B 3. C 4. D 5. E

B

Which cyclin increases during G2 to prepare for mitosis?

B

A mutation in p53 is likely to lead to cancer because

Cell will not repair DNA damage effectively due to lack of cell cycle arrest

11. Which step in the post-translational processing of fibrous collagen occurs outside the cell, following secretion? A. Cleavage of propeptides B. Cleavage of signal peptide C. Hydroxylation of proline to 4-OH proline D. Formation of triple helix E. Addition of sugar groups

Cleavage of propeptides

The following cyclin Cdk complex phosphorylates the ORC complex and triggers DNA winding, replication initiation while at the same time preventing re-replication

Cyclin A-Cdk2

target of the APC

Cyclin B

APC is a ubiquitin ligase that causes the degradation of:

Cyclin B Cdk1, Proteins that keep sister chromatids together ( Securin / separase)/Anaphase inhibitor

Cells transfected with two fusion proteins

Cα -CFP Cβ -YFP

binds to Adenylyl cyclase differently resulting in different activity

Cα subunit

membrane bound

DAG

We discussed an experiment in class that compared the cell cycle profile of cells with wild type p53 and p53 null ( knockout) cells at 8 hours after irradiation with gamma rays. In this experiment the cells were sorter based on their:

DNA content

APC or anaphase promoting complex has the following enzymatic activity

E3 ubiquitin ligase activity

For insulin receptor,

Each half contains an α and β subunit. β subunit autophosphorylate each other upon Insulin binding

Experimental analysis of Activation of G proteins occurs within seconds of ligand binding - using

FRET

The "restriction" or "commitment" point of the cell cycle refers to the point at which:

Further growth factor stimulation is no longer required to promote cell cycle progression

Mitogens are added to the medium of cultured human cells that are synchronized in mitosis. The mitogen is washed way after these cells have passed the restriction point in the cell cycle. These cells will progress through the cell cycle then arrest in which phase?

G0-G1 phase

Inactivator protein

GAP

Hormone permits __________ to be released So that ________can bind

GDP, GTP

Activator Protein

GEF

___________________catalyzed by the intrinsic GTPase activity of the α subunit

GTP hydrolysis

______________of alpha subunit turns signaling pathway off and dissociation of alpha from target protein.

GTPase activity

Major classes of Plasma Membrane receptors

Gated ion Channels, G Protein-coupled receptors, Tyrosine kinase receptors, Jak-STAT coupled receptors, Serine/Threonine kinase receptors, Guanyl cyclase receptors

Inhibitory, inhibits adenyl cyclase

Gi

Stimulatory, acts on phospholipase

Gq

Jak-STAT coupled receptors

Growth hormone, Prolactin, interferons, many cytokines

Stimulatory, activates adenyl cyclase

Gs

The following are the negative regulators of the cell cycle and specifically inhibit Cdk4 and Cdk6 activity

INK4 class of proteins

diffuses way

IP3

Downstream events referred to

IP3/DAG pathway

34. The role of retinoblastoma protein (Rb) in regulation of the cell cycle is best characterized as: a. Inhibits transcription of critical genes by complexing with E2F transcription factors b. Activates transcription of critical genes by complexing with E2F transcription factors c. Activates cyclin dependent kinases d. Inhibits cyclin dependent kinasese. Promotes cyclin degradation

Inhibits cyclin dependent kinasese. Promotes cyclin degradation

The role of retinoblastoma protein (Rb) in regulation of the cell cycle is best characterized as:

Inhibits transcription of critical genes by complexing with E2F transcription factors

Tyrosine kinase receptors

Insulin, growth factors such as epidermal growth factor EGF, and others

The period of DNA synthesis in continually dividing mammalian cells occurs: a. Just after mitosis b. Just before mitosis c. Is separated from the preceeding and the following mitosis by Gap periods d. Continuously dividing cells do not replicate their DNA

Is separated from the preceeding and the following mitosis by Gap periods

Guanyl cyclase receptors

NO, Natriuretic peptide

Eicosanoids

PGs, thromboxanes, leukotrienes

IP3/DAG pathway and the elevation of cytosolic Ca2+

Phosphoinositide coupled GPCR

endocrine system

Polypetide-Insulin, and catecholamines (also neurotransmitters) -bind to plasma membrane receptors to initiate action. Steroid hormones (cortisol)

The ____________________ contains an intrinsic protein tyrosine kinase catalytic site

RTK cytosolic domain

receptor associated kinase

RTKs, TGFB, cytokine, jak-stat, Ras/map kinase

Cyclins function as:

Regulatory modulators of protein kinases

33. Cyclins function as: a. Protein kinases b. Transcription factors c. Protein phosphatases d. Regulatory modulators of protein kinases called CDK's

Regulatory modulators of protein kinases called CDK's

All the following statements about destruction of cyclins are true, except:

Ubiquitin targets Cdks.

DNA replication at each origin occurs only once during the cell cycle because of:

S phase Cdk phosphorylating MCM helicase & cdc6.

The activated kinase phosphorylates several tyrosine residues in the receptor's cytosolic domain, which provides docking sites for _______domain containing proteins (in target or adaptor molecules).

SH2

The _____ domain in GRB2, an adapter protein, binds to specific phosphotyrosine residues in activated RTKs. The two _____ domains of GRB2 then bind ______, a guanine nucleotide exchange factor, thereby bringing it close to membrane-bound ___________ and activating its exchange function

SH2; SH3; SOS;

The estrogen receptor is a transcription factor that illustrates: A. Direct activation of the promoter without need for additional proteins B. Activation from a MAP kinase cascade C. Switch between an activator or silencer depending on the ligand bound D. Use of a homeodomain type DNA binding domain

Switch between an activator or silencer depending on the ligand bound

Growth Factors

TGF-β, BMP

Immunesystem

TNF, many cytokines, chemotactic cytokines, CSF, interleukins

Which of the following characteristics of steroid hormone receptors are shared by both type I and type II receptors? A. The receptor is always located in the nucleus. B. The receptor only binds to the response element when bound by hormone. C. The binding of hormone is required for transcriptional activation. D. All of the choices are correct.

The binding of hormone is required for transcriptional activation

Which one of the following statements about indirect response such as that by G-protein coupled receptor-regulation of adenylate cyclase is correct?

The cAMP generated by adenylate cyclase is the second messenger.

Which of the following characteristics of steroid hormone receptors are shared by both type I and type II receptors? A. The receptor is always located in the nucleus. B. The receptor only binds to the response element when bound by hormone .C. The direct binding of hormone is required for transcriptional activation. D. All of the choices are correct.

The direct binding of hormone is required for transcriptional activation.

Caspases play what role(s) in the cell?

They are proteases that cleave next to aspartic acid to trigger apoptosis

Serine/Threonine kinase receptors

Transforming Growth Factor b, Bone Morphogenic Proteins

Mad's and Bub's are part of the checkpoint control that is sensitive to:

Unattached kinetochores (centromere) in mitosis, Monotelic attached kinetochores in mitosis

A constitutive high-level expression of c-fox or c-jun in cells will lead to

activation of cdk4/6 activity in the absence of growth factors

In paracrine signaling, the signaling molecule

acts on cells in proximity to the secreting cell.

Because Second messengers diffuse through the cytosol faster than proteins, this facilitates

amplification of an extracellular signal

Nervous system

biogenic amines and neuropeptides

two types of nervous system chemical signals

biogenic amines and neuropeptides

the synthetic pathways leading to AMP and GMP are ____________ a)linearly related with GMP being produced first then converted to AMP b) branched at the level of an intermediate that can be converted into either GMP or AMP c) linearly related with AMP produced first then GMP d) independent of each other, using separate precursors

branched at the level of an intermediate that can be converted into either GMP or AMP

hydrolyzes cAMP to 5'-AMP

cAMP phosphodiesterase

The phenomenon of catabolite repression refers to a situation in which the presence of glucose in the growth medium results in lowered levels of beta-galactosidase ( lac Z) , even when lactose is also present. Which aspect of the lac operon and its controlling factors is most directly related to catabolite repression? I. Lactose permease J. Operator region K. Lac repressor protein L. cAMP response protein M. Allo-lactose

cAMP response protein

G Protein-coupled receptors

catecholamines, prostaglandins

Receptors themselves have Tyrosine kinase activity: bind JAK- tyr kinase

no

Cisplatin is a mutagen that causes chemical reactions that the cell cannot easily repair nevertheless, cisplatin is used to fight many cancers. the logic is that

cisplatin is an alkylating agent, blocks replication forks

Signal transduction begins with a

conformational change

13. Eukaryotic proteins do not require a targeting signal if they are destined to function in the: A. nucleus. B. lysosome. C. plasma membrane. D. cytoplasm.

cytoplasm

In the same experiment mentioned above, it was observed that p53 null (mutant) cells

did not show a G1 arrest

The type of signaling in which the signal producing cell is located at a far distance from the target cell and the signal travels through the blood stream is called _______ _________

endocrine signaling

4 types of extracellular signaling

endocrine, paracrine, autocrine, signaling by plasma attached membranes

order of amplification top to bottom

epinephrine, adenylyl cyclase, cAMP, protein kinase A, activated enzyme, product

Second messengers diffuse through the cytosol ________ than proteins

faster

unusual in that it exists as a dimer in the non-activated state and that it has special signal transduction partners

insuline receptor

After association with arrestins, GPCRs can be trafficked to _________________where they are ultimately degraded or to recycling endosomes for recycling back to the cell surface in the functional process of resensitization — whereby the cell is resensitized for another round of signali

lysosomes

What are the 6 types of chemical signals?

nervous system, endocrine system, hormones, immune system, eicosanoids, Growth Factors

Four common intracellular second messengers

pka, pkg, DAG, IP3

Degradation

proteasome

the mechanism by which insulin signaling is terminated includes: a) change in temperature b) the aggregation of all protein units c) degradation of insulin receptor d) protein dephosphorylation by phosphatases

protein dephosphorylation by phosphatases

DAG (diacyl glycerol) enhances activity of

protein kinase C

___________ is/are necessary for the cellular reception of biological signals a)ATP b) protein phosphatases c) receptors d) ion channels e) protein kinases

receptors

JAK2 deactivation by SHP1 phosphatase

short- term regulation

signal blocking and protein degradation by SCOS

short-term regulation

hormones

some not produced by Endocrine cells: Retinoids, VitaminD

In Jack-Stat, __________where they serve as transcription factors via specific DNA binding elements

stats

which statement about steroid hormones is true? a) 7TM receptors change their conformation upon binding to steroid hormones b) steroid hormones activate G-protein cascades c) steroid hormones activate receptors in the cell membrane d) steroid hormones directly regulate protein synthesis e) steroid hormones bind to nuclear receptors to activate gene expression

steroid hormones bind to nuclear receptors to activate gene expression

The role of p53 in regulation of the cell cycle can be characterized as

stimulates transcription of genes for cyclin inhibitory proteins

Another case in which signal transduction involves direct activation of latent transcription factors

the Smads

There are a class of proteins (e.g., p21 and INK4) that are negative regulators of the cell cycle and specifically inhibit Cdk activity.(t/f)

true