title: RTK SLAP down: the emerging role of Src-like adaptor protein as a key player in receptor tyrosine kinase signaling.
abstract: SLAP (Src like adaptor protein) contains adjacent Src homology 3 (SH3) and Src homology 2 (SH2) domains closely related in sequence to that of cytoplasmic Src family tyrosine kinases. Expressed most abundantly in the immune system, SLAP function has been predominantly studied in the context of lymphocyte signaling, where it functions in the Cbl dependent downregulation of antigen receptor signaling. However, accumulating evidence suggests that SLAP plays a role in the regulation of a broad range of membrane receptors including members of the receptor tyrosine kinase (RTK) family. In this review we highlight the role of SLAP in the ubiquitin dependent regulation of type III RTKs PDGFR, CSF-1R, KIT and Flt3, as well as Eph family RTKs. SLAP appears to bind activated type III and Eph RTKs via a conserved autophosphorylated juxtamembrane tyrosine motif in an SH2-dependent manner, suggesting that SLAP is important in regulating RTK signaling.
authors.affiliation: The Arthur and Sonia Labatt Brain Tumour Research Centre and Program in Cell Biology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada, M5G 1X8. Electronic address: leanne.wybenga.groot@utoronto.ca.
authors.forename: Leanne E
authors.initials: LE
authors.lastname: Wybenga-Groot
authors.affiliation: The Arthur and Sonia Labatt Brain Tumour Research Centre and Program in Cell Biology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada, M5G 1X8; Department of Medical Biophysics, University of Toronto, 610 University Avenue, Toronto, ON, Canada, M5G 2M9. Electronic address: jmcglade@sickkids.ca.
authors.forename: C Jane
authors.initials: CJ
authors.lastname: McGlade
mesh_terms: D006801:Humans; D019009:Proto-Oncogene Proteins c-kit / Q000737:chemistry / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000737:chemistry / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D051941:fms-Like Tyrosine Kinase 3 / Q000737:chemistry / Q000378:metabolism; D018909:src Homology Domains
chemical_list: D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases; D016186:Receptor, Macrophage Colony-Stimulating Factor; D020797:Receptor, Platelet-Derived Growth Factor beta; D051941:fms-Like Tyrosine Kinase 3; D016392:Proto-Oncogene Proteins pp60(c-src)
keywords: Cbl; Eph; Juxtamembrane; Regulation; SLAP2