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 differentiation. The intracellular signaling pathways that mediate these important processes are not well understood. In Caenorhabditis elegans, suppressors of clr-1 identify genes, termed soc genes, that potentially mediate or activate signaling through the EGL-15 FGF receptor. We demonstrate 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 putative human homolog, SHOC-2, which is 54% identical to SOC-2. We find that shoc-2 maps to 10q25, shoc-2 mRNA is expressed in all tissues assayed, and SHOC-2 protein is cytoplasmically localized. Within the leucine-rich repeats of both SOC-2 and SHOC-2 are two YXNX motifs that are potential tyrosine-phosphorylated docking sites for the SEM-5/GRB2 Src homology 2 domain. However, phosphorylation of these residues is not 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 conserved gene implicated in mediating FGF receptor signaling in C. elegans.
Selfors
L M
LM
Department of Biology, Yale University, P.O. Box 208005, New Haven, CT 06520-8005, USA.
Schutzman
J L
JL
Borland
C Z
CZ
Stern
M J
MJ
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins; D005346:Fibroblast Growth Factors / Q000378:metabolism; D017238:Genes, Helminth; D016153:Genes, Suppressor; D015801:Helminth Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007930:Leucine; D008969:Molecular Sequence Data; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D016415:Sequence Alignment; D015398:Signal Transduction / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; D047908:Intracellular Signaling Peptides and Proteins; D017468:Receptors, Fibroblast Growth Factor; D012097:Repressor Proteins; C112913:SHOC2 protein, human; C113520:soc-2 protein, C elegans; D005346:Fibroblast Growth Factors; D007930:Leucine