Reactome | STAP2 recruits STAT3 to PTK6

STAP2 recruits STAT3 to PTK6

Stable Identifier

R-HSA-8848087

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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STAP2 binds to STAT3 and promotes STAT3 activation (Ikeda et al. 2009, Minoguchi et al. 2003). Phosphorylation of STAP2 at tyrosine residue Y250 (Minoguchi et al. 2003, Ikeda et al. 2009) and possibly also Y322 (Minoguchi et al. 2003) is needed for STAT3 binding. Phosphorylation of STAP2 by PTK6 at tyrosine Y250 enables STAP2 to simultaneously interact with PTK6 (BRK) and STAT3, thus recruiting STAT3 to PTK6 (Ikeda et al. 2009, Ikeda et al. 2010). The pleckstrin homology (PH) domain of STAP2 binds to PTK6, while the SH2 domain and the C-terminus of STAP2 interact with STAT3 (Ikeda et al. 2010).

STAP2 may promote nuclear translocation of PTK6, which could be dependent on STAT3 binding (Ikeda et al. 2010). STAP2 protein levels are negatively regulated by the E3 ubiquitin ligase CBL. CBL can form a complex with STAP2, but the direct ubiquitination of STAP2 by CBL has not been demonstrated (Sekine et al. 2009). PTK6, on the other hand, promotes CBL protein down-regulation (Kang and Lee 2013).

Literature References

PubMed ID	Title	Journal	Year
19393627	STAP-2 is phosphorylated at tyrosine-250 by Brk and modulates Brk-mediated STAT3 activation Miyasaka, Y, Matsuda, T, Mizushima, A, Nanbo, A, Ikeda, O, Sekine, Y, Muromoto, R, Yoshimura, A	Biochem. Biophys. Res. Commun.	2009
20929863	Interactions of STAP-2 with Brk and STAT3 participate in cell growth of human breast cancer cells Miyasaka, Y, Matsuda, T, Mizushima, A, Nanbo, A, Ikeda, O, Sekine, Y, Nakasuji, M, Muromoto, R, Yamamoto, C, Yoshimura, A, Oritani, K	J. Biol. Chem.	2010
12540842	STAP-2/BKS, an adaptor/docking protein, modulates STAT3 activation in acute-phase response through its YXXQ motif Minoguchi, S, Matsuda, T, Yumioka, T, Yamamoto, T, Minoguchi, M, Aki, D, Yoshimura, A, Joo, A	J. Biol. Chem.	2003