The Role of the Src-like Adaptor Protein in the Regulation of GM-CSFR Signaling

GM-CSF is a cytokine that regulates proliferation and survival of myeloid progenitor cells and stimulates dendritic cell (DC) differentiation. The Src-like adaptor protein (SLAP) has been implicated in the negative regulation of the GM-CSF receptor and downstream signaling in DC, although the mechanism of SLAP action remains unknown. We hypothesized that SLAP regulates GM-CSFR by recruiting CBL to the receptor, where it can ubiquitylate and target it for degradation. In this investigation we found that SLAP interacts with both SHP2 and CBL in a GM-CSF dependent manner and that SLAP and CBL over-expression alters GM-CSFR trafficking. SLAP is also important in regulating GM-CSF-stimulated DC development. In this study we determined that the role of SLAP in regulation of GM-CSF signaling is specific to differentiation in DC and we identified differentially expressed genes in Slap knock-out DC that may be important for maturation.M.Sc.2016-11-30 00:00:0