SOC-2 ENCODES A LEUCINE-RICH REPEAT PROTEIN IMPLICATED IN FIBROBLAST GROWTH-FACTOR RECEPTOR SIGNALING

Activation of fibroblast growth factor (FGF) receptors elicits diverse cellular responses including growth, mitogenesis, migration, and diff erentiation. The intracellular signaling pathways that mediate these i mportant processes are not well understood. In Caenorhabditis elegans, suppressors of clr-1 identify genes, termed soc genes, that potential ly mediate or activate signaling through the EGL-15 FGF receptor. We d emonstrate that three soc genes, soc-1, soc-2, and sem-5, suppress the activity of an activated form of the EGL-15 FGF receptor, consistent with the soc genes functioning downstream of EGL-15. We show that soc- 2 encodes a protein composed almost entirely of leucine-rich repeats, a domain implicated in protein-protein interactions. We identified a p utative human homolog, SHOC-2, which is 54% identical to SOC-2, We fin d that shoc-2 maps to 10q25, shoc-2 mRNA is expressed in all tissues a ssayed, and SHOC-2 protein is cytoplasmically localized. Within the le ucine-rich repeats of both SOC-2 and SHOC-2 are two YXNX motifs that a re potential tyrosine-phosphorylated docking sites for the SEM-5/GRB2 Src homology 2 domain. However, phosphorylation of these residues is n ot required for SOC-2 function in vivo, and SHOC-2 is not observed to be tyrosine phosphorylated in response to FGF stimulation. We conclude that this genetic system has allowed for the identification of a cons erved gene implicated in mediating FGF receptor signaling in C. elegan s.