Question

A single transmembrane hormone receptor associates into a dimer upon binding to the hormone on the exterior of the cell. The cytoplasmic domains of the receptor dimer have tyrosine kinase activity and each subunit of the dimer phosphorylates tyrosines in the other subunit. These phosphorylated tyrosines then serve as substrates for the binding of a membrane associated protein Xm. Upon the binding of Xm to the phosphorylated transmembrane dimer, the kinase activity of the dimer also phosphorylates the Xm protein which activates it to continue the signal transduction pathway.

1. Describe the domains that the protein Xm might contain that would allow it to be membrane associated and to recognize and bind to the receptor dimer but not the receptor monomer.
2. What domain(s) would you expect to find in the receptor?
3. Describe the series of events that would be necessary for the activated hormone dimer complex to return to its inactive monomeric state.
   1. Would you expect the rate of this recovery (Active receptor conversion to inactive receptor) to be faster or slower than the recovery for a hormone bound 7 transmembrane receptor protein with it’s associated trimeric G-proteins? Provide a rationale for your answer.

Answer 1

A > Protein Xm contain SH2 domain this domain recognizes phosphotyrosine residue on cytosolic receptors.

Because receptors remain monomer and un phosphorylated until hormones not bound to extracellular domain.

after hormone binding receptor get dimerised and autophosphorylate to each other on cytosolic domain.

Now SH2 domain able to bind on phosphotyrosine of cytosolic receptor domain.

SH2 domain faund in STAT protein.

B > Domains of receptor..

All receptors have essentially three components -

Extra cytosolic ligand binding domain

A hydrophobic transmembrane alpha helical segment.

And an cytosolic domain which contain protein tyrosine kinase activity in RTK.

Serine and threonine residue in c- terminal segment of G-protein.

Phosphorylated serine and threonine residue recruited by arresting protein.

C >

For the regulation of receptor tyrosine kinase activity GPCR there is endocytosis mechanism in which activated HER1 receptor (RTK) recruited by Catherine pits and Endocytosised and degraded in endosome.

For termination of signal transduction in cytokine receptor there is 2 process..

Short term regulation

A SHP1 phosphatase removes phosphate from cytosolic domain and makes it inactive.

lond term regulation

Socs protein responsible for long term termination.. Which removes phosphate degrades JAK 2 kinase.

D >

Prolonged treatment of cells with ligand often reduces the number of available cell-surface receptors such that the cells will have a less response to exposure to a given concentration of ligand than they did before the treatmen.

Unbound ligand receptor are internalized very slowly and coming back on the cell surface very fast.

But prolanged treatment of harmone end product of GPCR that is PKA( protein kinase A) phosphorylate serine and threonine residue on the c-terminal domain of the receptor.

And receptor also phosphorylated by an another kinase BARK beta adrenergic receptor kinase.

These phosphorylated receptor recognize by beta arrestin and Catherine pits and causes receptor Internalization.

These ligand boun receptor internalize very fast but

Come back on cell surface with very slow rate.