Question

Receptor Tyrosine Kinases and Ras

a. Describe the events that occur upon ligand binding to receptor kinase receptors.

b. Describe the similarities and differences in the cycling of Gs and Ras between the active and inactive forms.

c. Describe the kinase cascade that transmits signals down from activated Ras.

Answer 1

a. When a ligand binds to receptor kinase receptors it will activate the kinase. If kinase is a monomer it becomes dimer overcoming auto inhibition by extracellular receptoe binding site, (or) if it exists as pre existing dimer after kinase activation dimerization is stabilized. When kinase is activated auto phosphorylation takes place.

b. Similarities and differences in the cycling of Gs and Ras between the active and inactive forms.

Siimilarity:

1.Ras release an inorganic phosphate and binds to GDP. GDP-bound form is considered inactive,

In the inactive form Gs (G protein sub unit) is attached to GDP and G to produce an inactive trimer.

2. Ras and Gs both are activated by GTP.

Difference:

1. Ras activates protein kinase and Gs activates Adenylyl cyclase in the active form.

c. When a ligand binds to the receptor it activates the kinase.

Kinase causes dimerization if it exists as monomer or if it already exists as a dimer the dimerization gets stabilized by the auto phosphorylation of tyrosine residue in the intracellular part.

This phosphorylation activates an adapter molecule Grb-2 which binds to the Receptor Tyrosine kinase and then activates SOS, now SOS binds to Grb-2 which eventually attaches to the RTK. . Here Grb-2 acts as an adapter molecule for SOS to bind to RTK.

After binding of SOS to RTK,ot activates Ras which is a GTPase. Here, Ras makes GDP into GTP and then eventually activates Raf which activates MAP K also known as ERK which travels into the nucleus and initiates transcription.