Hox12 and Hox13 paralogues specify the autopod.

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#Unit 4. Cell Communication and Cell Signaling

NGF, PDGF, FGF, EGF, insulin are RTK ligands, which trigger proliferation of cells.

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#Unit 4. Cell Communication and Cell Signaling

The cytosolic domain of RTKs contains an intrinsic protein tyrosine kinase domain.

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#Unit 4. Cell Communication and Cell Signaling

Cytosolic kinase domain of an RTK contains a flexible domain termed activation loop. 

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#Unit 4. Cell Communication and Cell Signaling

In resting state,  the activation loop is not phosphorylated and assumes a conformation that blocks kinase activity.

In insulin receptor, it prevents binding of ATP. 

In FGF receptor, it prevents binding of substrate.

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#Unit 4. Cell Communication and Cell Signaling

For most, but not all, RTKs, the weakly active kinase in each subunit is phosphorylate a key tyrosine in the activation loop of the other subunit (trans-phosphorylation)

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#Unit 4. Cell Communication and Cell Signaling

Phosphorylation leads to a conformational change in the activation loop that unblocks kinase active site by reducing the Kd for ATP or the substrate to be phosphorylated.