Signaling-3

Question 1

Explain the cascade for a1 receptor action and mention other example with similar mechanism

Answer 1

When hormone binds to the serpenntine receptor it forms hormone-receptor complex that catalyzes GTP-GDP exchange on Gq. Which dissociates from bg and activates PLC, that cleaves PIP2 into IP3 & DAG. IP3 enters ER where it activates gated calcium channels that activates protein kinase C. DAG is hydrophobic and remains in memebrane & cooperates with Ca for activation of PKC. PKC phosphorylates target proteins. Ca can act directly of after binding calmodulin.
A1 adrenergic CAs, vaspressin & oxytocin

Question 2

Calmodulin requires….Ca ions for full occupancy

Answer 2

4

Question 3

Describe use & mechanism of action of phorbol ester

Answer 3

Synthetic tumor promoter
Similar to DAG but not rapidly metabolised continuously activates PKC leading to inference with the normal regulation of cell growth & division.

Question 4

The composition of inslin receptor is……, unlike GF receptors it is a ……

Answer 4

Heterotetramer (dimer ab+ab)
Dimer

Question 5

Describe the cascade of insulin receptor action

Answer 5

1. When insulin binds its receptor (a subunits) this leads to activation of tyrosine kinase activity of intracellular b subunit.
2. Cross-autophosphorylation of b subunits occurs leading to exposing active sites which can phosphorylate tyrosine of target proteins
3. For example insulin receptor substrates which activate kinases & phosphatases leading to the biologic actions of insulin

Question 6

Rapid actions of insulin are…. While delayed are……

Answer 6

Dephosphorylation of enzymes & inc no of GLUT-4 in membrane of muscle & adipose tissue
Gene expression & growth effects

Question 7

The actions of insulin are terminated by……

Answer 7

Dephosphrylation of the receptor

Question 8

Classify causes of insulin resistance

Answer 8

1. Pre-receptor causes: abnormal insulin or anti-insulin antibodies
2. Receptor causes: decreased no of receptors (failure of activation of tyrosine kinase), reduced binding, mutated receptor, insulin receptor-blocking Abs
3. Post-receptor causes: defective signal transduction, mutations of GLUT4

Question 9

Describe the cascade of JAK-STAT pathway

Answer 9

1. As the hormone binds to these receptors they form dimers, the receptor is activated and each monomer can now bind & activate a soluble tyrosine kinase called JAK
2. 2 active JAKs phosphorylate each other and then can bind STATs (signal transducer & activator of transciption)
3. STATs are phophorlated by bound JAK then two of them dimerize thus an activated transciption factor is formed.
4. STAT dimer translocates to nucleus and binds to hormone response element regulating gene transcription.

Question 10

Give examples for hormones utilizing the following pathways:
1. cAMP
2. PIP2
3. Intrinsic Tyrosine kinase activity

Answer 10

1. Glucagon, epinepherine (b), vasopressin on kidney (V2, ADH)
2. Vasopressin on vascular smooth muscle (V1, V3), epinepherine(a1)
3. Insulin, IGF, PDGF, EGF