Cell signalling

How does termination of cellular response at the ligand receptor binding stage occur?

Fo.r the ligand receptor interaction stage: Extracellular ligands can be degraded by enzymes to prevent the ligands from binding to their specific receptors again to trigger signal transduction. The ligand-receptor complexes can be endocytosed into the cell and targeted by lysosomes for degradation. Receptors can be endocytosed into the cell to remove the receptors from the cell surface membrane to prevent ligands from binding.

How does termination of cellular response at the signal transduction stage occur?

For the signal transduction stage: Dephosphorylation of relay proteins to deactivate these proteins and thus prevent the propagation of signals along the signal transduction pathway. Second messengers can be degraded by enzymes to prevent activation of their target molecules.

How is cellular response terminated to prevent overstimulation for the case study if G protein linked receptor

G protein contains GTPase activity where GTP is hydrolysed to GDP g protein is inactive when bound to GDP the g protein also dissociates from the enzyme causing the enzyme to be inactive again

General scheme for activation of G protein linked receptors Step 1

G protein linked receptor is inactive and the GDP bound G protein is inactive Step 1: Ligand receptor interaction Ligand bonds to the ligand binding site of the G protein linked receptor due to complementary shape Binding results in conformational changes in therefore exposing the cytosolic G protein binding domain The receptor is activated

Advantage and significance of cell signalling pathways.

1.Signal amplification, where small quantities of ligand are sufficient to bring about a very large cellular response. 2.Interaction/cross-talk between different signaling pathways allows for regulation or control of cellular response. 3.Specificity of cell signaling, where the the interaction between a receptor and its complementary ligand ensures the appropriate response from its target cell. 4.Hydrophilic ligands are able to activate gene expression in the nucleus even though these molecules cannot traverse the hydrophobic plasma membrane. This allows for transmission of signal across membrane barriers. 5.Single signal molecule can trigger multiple responses. The use of the same protein in more than one pathway allows cells to economize on the number of different proteins it must make. 6. Activation of many cells simultaneously, where a single signal molecule can activate multiple cell/cell types to give a coordinated response within body. 7. Signals can be terminated to prevent unintended prolonged cellular responses which may be harmful.

Ad and sig no.2

2.Interaction/cross-talk between different signaling pathways allows for regulation or control of cellular response.

Ad and sig no.6

6. Activation of many cells simultaneously, where a single signal molecule can activate multiple cell/cell types to give a coordinated response within body.

A cell can have different types of cell surface receptors. Do you think it is possible for the same cell to produce the same cellular response to different types of extracellular ligands? Can you justify your answer?

Yes, the same cell can produce the same cellular response to different extracellular ligands. It is possible for different signal transduction pathways to converge and activate the same final relay molecules that produce the same final cellular response.

You have learned that a specific extracellular ligand can only bind to a specific cell surface receptor in order to trigger signal transduction and cellular response. Different cell types can have the same cell surface receptors for binding the same extracellular ligand. Do you think it is possible to have different cellular responses in each of these different cell types? Can you justify your answer?

Yes, these different cell types can have different cellular responses when the same ligand binds to the receptor. It is possible because different cell types can contain different sets of relay molecules in the cytosol to result in different signal transduction pathways.

Activation of the G protein linked receptor step 2 Signal transduction

-G protein binds to the cytosolic G protein binding site -Exchange of GDP for GTP occurs -Gtp bound G protein is activated -G protein dissociates from the receptor and moves along the cell surface membrane -G protein binds to and activated and enzyme (relay molecule) -Activated enzyme can trigger the next step in the pathway leading to cellular response

activation of receptor tyrosine kinase signal transduction

1. Fully activated receptor polypeptide is recognised by specific relay proteins 2. each relay proteins binds to a specific phosphorylated tyrosine and undergoes a conformational change that activates relay protein 3. Different activated relay protein bind to their respective target protein to trigger different transduction pathways leading to specific cellular responses

glucagon signal transduction pathway signal transduction

1. G protein binds to the G protein binding domain of the GPLR 2. GDP is exchanged for GTP 3. the GTP bound G protein is active. 4. The G protein then dissociates from the GPLR and moves along the CSM. 5. The G protein binds to adenyl cyclase and activates it Adenyl cyclase catalyses the conversion of ATP to cAMP. 6. Each adenyl cyclase converts a large number of ATP to cAMP hence amplifying the signal. 7. cAMP acts as a second messenger and activates protein kinase A. 8. Each activated protein kinase A activates phosphorylase kinase which activates a large number of glycogen phosphorylase

activation of receptor tyrosine kinase ligand recpetor interaction

1. binding of ligand to the ligand binding site cause the 2 receptor polypeptides to dimerize 2. dimerization activates the tyrosine kinase domains of each receptor polypeptide 3. Each tk transfer phosphates from atp to tyrosine residues on the cytoplasmic tail of the other receptor polypeptide AKA AUTO-CROSS PHOSPHORYLATION they phosphorylate each other tyrosine residues on their cytoplasmic tails

glucagon signal transduction pathway ligand receptor interaction

1. glucagon binds to the ligand binding site of the GPLR on the csm of the effector cell. 2. this causes a conformational change in the GPLR, 3. exposing the cytosolic G protein binding domain of the GPLR. 4. The receptor is activated

glucagon signal transduction pathway cellular response

1. glycogen phosphorylase catalyses the conversion of a large number of glycogen to glucose-1-phosphate 2. leading to an increase breakdown of glycogen in the liver to produce glucose. 3. Allowing blood glucose level to increase back to the norm. The number of activated product is always greater than those in the preceding step as one moves down the cascade binding of one glucagon molecule to a single receptor will lead to the hydrolysis of a large number of glycogen to glucose

Ad and sig no.1

1.Signal amplification, where small quantities of ligand are sufficient to bring about a very large cellular response.

general info on receptor tyrosine kinases

1.transmembrane receptor that has kinase enzymatic activity allowing it to transfer phosphate groups from ATP to tyrosine 2.before the binding of the ligand each receptor polypeptide exists as individual units 3. receptor consists of an extracellular domain that binds to signal molecules on the extracellular side 4. consist of a cytoplasmic tail which consist of a kinase domain and several tyrosine residues.

Ad and sig no.3

3.Specificity of cell signaling, where the the specific interaction between a receptor and its complementary ligand ensures the appropriate response from its target cell.

Ad and signo.4

4.Hydrophilic ligands are able to activate gene expression in the nucleus even though these molecules cannot traverse the hydrophobic plasma membrane. This allows for transmission of signal across membrane barriers.

Ad and sig no. 5

5.Single signal molecule can trigger multiple responses. The use of the same protein in more than one pathway allows cells to economize on the number of different proteins it must make.

Ad and signo.7

7. Signals can be terminated to prevent unintended prolonged cellular responses which may be harmful.

General structure of G=protein linked receptors

Consist of a single polypeptide that is folded and embedded in the cell surface membrane . Each receptor consist of 7 transmembrane domain which spans the membrane. Each of the transmembrane domain is made up of an alpha helix.The receptor consist of an extracellular domain that binds to signal molecules on the extracellular side and also consist of an intracellular domain that binds to the G-proteins on the cytoplasmic side. G protein linked receptors Cary in 3D conformational their binding sites for the ligand and. Different G proteins inside the cell.

CASE STUDY 1 ion receptor

Step 1 : ligand receptor interaction before the ligand binding, the ion channel is closed Step 2 :signal transduction Binding of the ligand to the receptor brings about a conformational change that results in the the opening of the ion channel Specific ion can flow through the channel and rapidly change the concentration of that particular ion within the cell This change may directly affect the activity of the cell in some way. Step 3: Cellular response When the ligand dissociates from the receptor the resulting change in the conformation closes the ion channel again, and ions no longer enter the cell. Change can be an increase or decrease in gene expression or the activation or deactivation of an enzyme

glucagon signal transduction pathway stimulus

the decrease in blood glucose concentration results in the release of the glucagon hormone from the alpha cells of the islets of langerhans in the pancreas glucagon is then carried via the bloodstream to the effector cells which are the liver and muscle cells