Reactome | MET activates STAT3

MET activates STAT3

Stable Identifier

R-HSA-8875791

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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The STAT3 transcription factor binds to activated MET through phosphorylated tyrosine residue Y1356 of MET. STAT3 may also bind to activated MET indirectly through GAB1, but this interaction has not been studied in detail. Activated MET induces phosphorylation of STAT3 at Y705, triggering STAT3 dimerization and nuclear translocation (Schaper et al. 1997, Boccaccio et al. 1998, Zhang et al. 2002, Cramer et al. 2005). Endocytosis of MET and interaction with STAT3 at endosomes may be required for sustained STAT3 phosphorylation in response to HGF stimulation (Kermorgant and Parker 2008). Activated SRC may also contribute to phosphorylation of STAT3 at Y705. STAT3 may promote HGF transcription in a SRC-dependent way, but this autocrine HGF loop may be limited to breast cancer cells (Wojcik et al. 2006, Sam et al. 2007). MET-mediated activation of STAT3 is implicated in anchorage independent cell growth and invasiveness downstream of HGF (Zhang et al. 2002, Cramer et al. 2005). MET can also interact with STAT1A, STAT1B and STAT5, but the biological importance of these interactions is not known (Runge et al. 1999).

Literature References

PubMed ID	Title	Journal	Year
18779368	Receptor trafficking controls weak signal delivery: a strategy used by c-Met for STAT3 nuclear accumulation Kermorgant, S, Parker, PJ	J. Cell Biol.	2008
15838885	Activation of the c-Met receptor complex in fibroblasts drives invasive cell behavior by signaling through transcription factor STAT3 Cramer, A, Kleiner, S, Westermann, M, Meissner, A, Lange, A, Friedrich, K	J. Cell. Biochem.	2005
9440692	Induction of epithelial tubules by growth factor HGF depends on the STAT pathway Boccaccio, C, Andò, M, Tamagnone, L, Bardelli, A, Michieli, P, Battistini, C, Comoglio, PM	Nature	1998
11803465	Requirement of Stat3 signaling for HGF/SF-Met mediated tumorigenesis Zhang, YW, Wang, LM, Jove, R, Vande Woude, GF	Oncogene	2002
9094433	Hepatocyte growth factor/scatter factor (HGF/SF) signals via the STAT3/APRF transcription factor in human hepatoma cells and hepatocytes Schaper, F, Siewert, E, Gómez-Lechon, MJ, Gatsios, P, Sachs, M, Birchmeier, W, Heinrich, PC, Castell, J	FEBS Lett.	1997
10558875	STAT 1alpha/1beta, STAT 3 and STAT 5: expression and association with c-MET and EGF-receptor in long-term cultures of human hepatocytes Runge, DM, Runge, D, Foth, H, Strom, SC, Michalopoulos, GK	Biochem. Biophys. Res. Commun.	1999
16407846	A novel activating function of c-Src and Stat3 on HGF transcription in mammary carcinoma cells Wojcik, EJ, Sharifpoor, S, Miller, NA, Wright, TG, Watering, R, Tremblay, EA, Swan, K, Mueller, CR, Elliott, BE	Oncogene	2006
17967179	A novel activating role of SRC and STAT3 on HGF transcription in human breast cancer cells Sam, MR, Elliott, BE, Mueller, CR	Mol. Cancer	2007