APS, an adaptor protein containing PH and SH2 domains, is associated with the PDGF receptor and c-Cbl and inhibits PDGF-induced mitogenesis

Role of protein ubiquitylation in regulating endocytosis of receptor tyrosine kinases

“…Comparably, Cbl has been shown to bind to specific tyrosine residues in CSF-1R, Met and ErbB2 (Klapper et al, 2000;Peschard et al, 2001;Wilhelmsen et al, 2002). cCbl can also bind to RTKs indirectly through adaptor proteins, such as Grb2-mediated binding to EGFR (Waterman et al, 2002), APS-mediated binding to PDGFR (Yokouchi et al, 1999b) and Grb2-and FRS2-mediated binding to FGFR (Wong et al, 2002a). Subsequently, Cbl is itself subject to tyrosine phosphorylation by EGFR at residue 371, which stimulates the ubiquitin ligase activity .…”

Tyrosine kinase oncogenes in normal hematopoiesis and hematological disease

“…In addition, Shp2 binds to Tyr-1009 in the C-terminal tail region, which serves as a docking site for Nckb as well . PLCgl and adaptor protein APS, which is able to associate with Cbl, interact with Tyr-1021 (Yokouchi et al, 1999). The adaptor protein Shc may interact directly through multiple tyrosine residues or indirectly via association with other tyrosine-phosphorylated proteins (Yokote et al, 1994).…”

SH2-B Family Members Differentially Regulate JAK Family Tyrosine Kinases

“…Lnk has been shown to play a pivotal role in the regulation of B cell production, as Lnk knockout mice show overproduction of pre-B cells in the spleen and pro-B cells in bone marrow (29). Overexpression of APS suppresses proliferation of NIH-3T3 cells as stimulated by platelet-derived growth factor (PDGF) (30). To date, the effects of APS and Lnk on the kinase activity and tyrosyl phosphorylation of JAKs have not been examined.…”