Activated MET receptor binds the complex of tensin-4 (TNS4) and integrin beta-1 (ITGB1). This interaction involves arginine residue R474 at the SH2 domain of TNS4 and phosphorylated tyrosines Y1349 and Y1356 of MET. Phosphorylated Y1313 of MET contributes to TNS4 binding but the kinase responsible for phosphorylation of MET at Y1313 is not known. TNS4, ITGB1 and MET co-localize at paxillin-positive focal adhesion sites. Binding of MET to TNS4 contributes to cell motility and promotes activation of AKT, but not ERK, downstream of MET. TNS4 is upregulated in colorectal, lung, ovarian and gastric cancer, with concomitant downregulation of TNS3. TNS4 and MET expression correlate in colorectal and ovarian cancer (Muharram et al. 2014).
De Franceschi, N,