Mutations in three broad classes of genes have been implicated in the onset of cancer. 

Protooncogenes

Tumor-suppressor genes

genome maintenance genes

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#Unit 4. Cell Communication and Cell Signaling

Cytokine receptors are stably associated with one or two of the four known JAKs:

JAK1, JAK2, JAK3, and Tyk2

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#Unit 4. Cell Communication and Cell Signaling

Each members of JAK family of kinases contains:

An N-terminal domain that binds to the receptor

A C-terminal kinase domain 

A middle pseudokinase domain

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#Unit 4. Cell Communication and Cell Signaling

JAK kinases become activated after ligand binding and

receptor dimerization

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#Unit 4. Cell Communication and Cell Signaling

Ligand binding triggers a conformational change in the JAKs & they phosphorylate each other on a critical tyrosine in the activation loop which greatly enhances kinase activity

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#Unit 4. Cell Communication and Cell Signaling

Active JAK kinase phosphorylates several tyrosine residues in the receptor’s cytosolic domain and activates a STAT transcription factor that moves directly to the nucleus

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#Unit 4. Cell Communication and Cell Signaling

All STAT proteins contain: 

an N-terminal DNA-binding domain

an SH2 domain

a C-terminal domain with a critical tyrosine residue