Keystone hypothesis

TLS Online TPP Program

#Id: 9638

#Unit 4. Cell Communication and Cell Signaling

Sos is a GEF that catalyzes conversion of inactive GDP bound Ras to the active GTP-bound form.

TLS Online TPP Program

#Id: 9639

#Unit 4. Cell Communication and Cell Signaling

GRB2 has- 

Phosphotyrosine-binding SH2 domain

Two SH3 domains, bind to Sos

TLS Online TPP Program

#Id: 9640

#Unit 4. Cell Communication and Cell Signaling

The SH3 domains in GRB2 selectively bind to 

proline-rich sequences in Sos

TLS Online TPP Program

#Id: 9641

#Unit 4. Cell Communication and Cell Signaling

Downstream of Ras is a highly conserved cascade of three protein kinases-

Ras → Raf → MEK → MAP kinase

TLS Online TPP Program

#Id: 9642

#Unit 4. Cell Communication and Cell Signaling

In unstimulated cells, 

Raf is phosphorylated by several cytosolic kinases on two sites:

1. Serine/threonine kinase domain 

2. N-terminal autoinhibitory domain

TLS Online TPP Program

#Id: 9643

#Unit 4. Cell Communication and Cell Signaling

Molecular Handcuff 

Phosphorylation of Raf is recognize by protein 14-3-3 dimer, which locks the autoinhibitory domain in a position where it blocks and inhibits the kinase active site