CELE_C14F5.5, C14F5.5

sem-5 encodes a Src homology (SH) domain 2 and 3-containing protein, orthologous to human GRB2 (OMIM:108355) and Drosophila Drk; sem-5 functions in multiple signaling pathways during development including those regulating sex myoblast migration, muscle membrane extension, vulval induction, fluid balance, viability, and formation of the male tail; SEM-5 acts downstream of the LET-23 epidermal growth factor receptor to negatively regulate RAS-, MAP-, and IP-3-, mediated signal transduction; a sem-5::yfp promoter fusion is expressed in many cells throughout development, including the hypodermis, intestine, neurons, body wall muscles, and vulval precursor cells.

CELE_Y18D10A.5, sgg-1, Y18D10A.5

gsk-3 encodes the C. elegans glycogen synthase kinase ortholog; during embryonic development, GSK-3 functions in the Wnt signaling pathway that restricts specification of mesendodermal tissue to the appropriate blastomere; GSK-3 also functions in a Wnt pathway that regulates anteroposterior axon guidance; GSK-3 plays a role in regulating the oocyte-to-embryo transition, by phosphorylating and negatively regulating the OMA-1 zinc finger protein, and in regulation of the oxidative stress response pathway by phosphorylating SKN-1, thereby excluding it from intestinal nuclei; GSK-3, along with MOM-5/Frizzled and APR-1/APC is also required for distal tip cell migration in the gonad and for the engulfment of apoptotic cells, indicating that the Wnt pathway signals to CED-10/Rac to regulate cytoskeletal rearrangement during different cellular processes; GSK-3 can be phosphorylated by murine ERK2 in vitro, suggesting that it is a substrate for the RTK-RAS-ERK pathway in vivo; consistent with this, GSK-3 phosphorylation is absent in mpk-1 mutant animals.