In the basal state, 

GAPs inhibit RalA and Rab10 function by enhancing their rates of GTP hydrolysis

TLS Online TPP Program

#Id: 9459

#XL - T Zoology

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

TLS Online TPP Program

#Id: 9461

#XL - T Zoology

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

TLS Online TPP Program

#Id: 9462

#XL - T Zoology

All STAT proteins contain: 

an N-terminal DNA-binding domain

an SH2 domain

a C-terminal domain with a critical tyrosine residue

TLS Online TPP Program

#Id: 9463

#XL - T Zoology

SH2 domain (Src homology 2 domain) 

homology with a region in the Src cytosolic tyrosine kinase encoded by the src gene.

TLS Online TPP Program

#Id: 9464

#XL - T Zoology

The SH2 domain binds strongly to short target peptides containing a critical four-residue core sequence:: 

phosphotyrosine–glutamic acid–glutamic acid–isoleucine

TLS Online TPP Program

#Id: 9466

#XL - T Zoology

Binding resembles the insertion of a two-pronged “plug” the phosphotyrosine and isoleucine side chains

of the peptide into a two-pronged “socket” in the SH2 domain.