Src-Like Adapter Protein (SLAP)
SLAP Gene and Protein
SLAP Interacting Proteins
A variety of proteins including cell surface receptors, membrane-bound non-receptor proteins, and cytosolic proteins bind with SLAP. Since a wide range of tissues express SLAP, it is likely that SLAP regulates multiple signaling cascades through interaction with various signaling molecules. SLAP has a myristoylated site near the N-terminus (G2), and thus it localizes to the cell surface where it interacts with several receptors including B-cell receptors (BCR), the T-cell receptors (TCR), platelet-derived growth factor receptor (PDGFR), stem cell factor receptor (KIT), FMS-like tyrosine kinase-3 (FLT3), EPH receptor A2 (EPHA2), and EPOR (Pandey et al. 1995; Roche et al. 1998; Tang et al. 1999; Manes et al. 2000; Lebigot et al. 2003; Kazi and Rönnstrand 2012; Kazi et al. 2014). Moreover, it has been shown that SLAP has a role in activation and maturation of monocyte and dendritic cells through downregulation of granulocyte macrophage colony-stimulating factor receptor (GM-CSFR) (Liontos et al. 2011). Besides receptors, SLAP binds to several intracellular kinases such as SYK, ZAP70 and LCK, the ubiquitin E3 ligase CBL, the guanine nucleotide exchange factor VAV1, and the SH2 domain-containing leukocyte protein SLP76 (Tang et al. 1999; Manes et al. 2000; Sosinowski et al. 2000; Hiragun et al. 2006; Park et al. 2009). Thus, SLAP plays important roles through the interaction of different types of proteins.
SLAP-Mediated Regulation of Cell Signaling
The adapter protein SLAP plays crucial roles in regulating receptor turnover by recruiting ubiquitin E3 ligases to the receptors. Therefore, SLAP is mainly involved in negative regulation of signaling downstream of receptors. However, there is also evidence that SLAP can enhance receptor downstream signaling, although the mechanism of this regulation has not been understood well. Our current knowledge about SLAP-mediated regulation is limited to mitogenesis, and future studies should address the role of SLAP in the regulation of different biological process including intracellular trafficking, cell cycle progression, and metabolism.