CGC Bibliography Paper 5135

Caenorhabditis elegans lin-45 raf is essential for larval viability, fertility and the induction of vulval cell

Hsu V, Zobel CL, Lambie EJ, Schedl T, Kornfeld K

Medline:

Citation:

Genetics 160: 481-492 2002

Type:

ARTICLE

Genes:

gon-2 let-60 lin-1 lin-12 lin-15 lin-31 lin-45 mek-2 mpk-1 sup-11 nDf41

Abstract:

The protein kinase Raf is an important signaling protein. Raf activation is initiated by an interaction with GTP-bound Ras, and Raf functions in signal transmission by phosphorylating and activating a mitogen-activated protein (MAP) kinase kinase named MEK We identified 13 mutations in the Caenorhabditis elegans lin-45 raf gene by screening for hermaphrodites with abnormal vulval formation or germline function. Weak, intermediate, and strong loss-of-function or null mutations were isolated. The phenotype caused by the most severe mutations demonstrates that lin-45 is essential for larval viability, fertility and the induction of vulval cell fates. The lin-45(null) phenotype is similar to the mek-2(null) and mpk-l(null) phenotypes, indicating that LIN-45, MEK-2, and MPK-1 ERR MAP kinase function in a predominantly linear signaling pathway. The lin-45 alleles include three missense mutations that affect the Ras-binding domain, three missense mutations that affect the protein kinase domain, two missense mutations that affect the C-terminal binding domain, three nonsense mutations, and one small deletion. The analysis of the missense mutations indicates that ras binding, 14-3-3-binding, and protein kinase activity are necessary for full Raf function and suggests that a 14-3-3 protein positively regulates Raf-mediated signaling during C.