PART I In addition to the EGFR carefully consider the insulin receptor as a prot

Question

PART I
In addition to the EGFR carefully consider the insulin receptor as a prototypical RTK.

- how does ligand-binding lead to receptor activation?

- how is the receptor itself and/or ligand-based activation different from the EGFR?

- describe one of the intracellular signaling pathways that lies downstream of insulin receptor activation; how is this particular pathway important for the overall physiology of the cell?

- how are these various branches of the insulin signaling cascade regulated? when does one branch get "turned on" as opposed to another, or when do they happen simultaneously & what controls this? what specific feedback mechanisms exist?

- how can dysfunctional insulin signaling contribute to disease?

Explanation / Answer

a) ligand mediated activation: the binding of small molecules (lignads) to the receptors causes allosteric transition in the receptor which causes the receptor to open or close.

b) EGFR is an RTK i.e. receptor tyrosine kinase based receptor.in which the alpha beta subunits of the receptors get phosphorylated in the cytosolic tyrosine regions in response to the binding of insulin in the extracellular domain. thus further activate the cascade of events. Ligand mediated activation, on the hand, causes activation of G-protein mediated cascade of events. binding of ligand to the receptor causes association of trimeric G-protein to the ligand receptor conjugate via G-alpha sub unit. the Gaplha has GDP (guanosine diphosphate) attached to it which is released and GTP (guanosine triphosphate) is bound now, this causes Galpha to dissociate from the G-betagamma subunit. when the ligand dissociates from the receptor. GTP hydrolyzes and GDP is bound and returns to the original state.

c)insulin binds to ts receptor on the extracellular domain.the receptor undergoes autophosphorylation at the tyrosine residue in the intracellular region of the receptor. these phosphorylated receptors in turn phosphorylate IRS-1 (Insulin receptor substrate 1) at its tyrosine residue. once phosphorylated it will in turn bind to the SH2 domain of the Grb2 protein. the Grb2 protein inturn binds to SOS protein which binds to Ras protein causing dissociation of GDP from Ras and replacement with GTP (this activates Ras protein). Ras will activate Raf-1. Raf 1 activates MEK via phosphorylation at ser residues.(MEK) is mitogen activating factor which in turn activated ERK via phosphorylation on thr and Tyr residue. ERK is then translocated into the nucleus where it phosphorylates Elk-1 and this Elk-1 then joins with SRF protein. this SRF-Elk1 conjugate will stimulate transcription and translation of genes needed for cell division.

d)inactive Glut -4 transporters causes diabetes

Related Questions

Navigate

• Browse (All)
• Browse P
• Subjects

Integrity-first tutoring: explanations and feedback only — we do not complete graded work. Learn more.