β-catenin binds to TCF to displace the Gro repressor and recruits co-activator proteins Pygo, LGS, to activate target gene expression.

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#Unit 4. Cell Communication and Cell Signaling

GRB2 has- 

Phosphotyrosine-binding SH2 domain

Two SH3 domains, bind to Sos

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#Unit 4. Cell Communication and Cell Signaling

The SH3 domains in GRB2 selectively bind to 

proline-rich sequences in Sos

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#Unit 4. Cell Communication and Cell Signaling

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

Ras → Raf → MEK → MAP kinase

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#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

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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

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#Unit 4. Cell Communication and Cell Signaling