Question

Explain the function of GEFs and GAPs and how one of these is relevant to signaling through RTKs and integrins. (4 pts)

Answer 1

GTPase-activating proteins (GAPs) regulatory proteins that facilitate the hydrolysis of bound GTP, resulting in the inhibition of the protein. The GTP exchange proteins (GEFs), facilitate the exchange of GTP for GDP, activating the protein. These two.proteins are the major affectors of the GPCR cascade and the RTK pathaways. Receptor Tyrosine Kinases are activated by Ras proteins that signal the downstream cascase. Ras is also a GAP and acts a switch.The activity of Ras GAPs and GEFs, leads to the activation of RTKs and id respinsible for downstream signal transmission. Two cytosolic adator proteins — GRB2 and Sos — are important transducers after RTK dimerisation. GRB2 binds to a specific phosphotyrosine residue in the activated receptor via their SH2 domain. GRB2 bind to and activate Sos via their SH3 domain. Thus, GRB2 functions as an adapter while Sos functions as a guanine nucleotide – exchange protein (GEF), which helps convert inactive GDP-bound Ras to the active GTP-bound form. Once this step is complete, MAP Kinases initiate further signaling.

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