title: Caenorhabditis elegans lin-45 raf is essential for larval viability, fertility and the induction of vulval cell fates.
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-1(null) phenotypes, indicating that LIN-45, MEK-2, and MPK-1 ERK 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 14-3-3 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. elegans development.
authors.affiliation: Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: Virginia
authors.initials: V
authors.lastname: Hsu
authors.forename: Cheri L
authors.initials: CL
authors.lastname: Zobel
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Lambie
authors.forename: Tim
authors.initials: T
authors.lastname: Schedl
authors.forename: Kerry
authors.initials: K
authors.lastname: Kornfeld
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D005260:Female; D005298:Fertility / Q000235:genetics / Q000502:physiology; D005804:Genes, Lethal; D007814:Larva / Q000235:genetics / Q000502:physiology; D008969:Molecular Sequence Data; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D016415:Sequence Alignment; D013489:Suppression, Genetic; D048490:raf Kinases
chemical_list: D029742:Caenorhabditis elegans Proteins; D017346:Protein Serine-Threonine Kinases; C454817:lin-45 protein, C elegans; D048490:raf Kinases