RRC ID 6315
著者 Arur S, Ohmachi M, Nayak S, Hayes M, Miranda A, Hay A, Golden A, Schedl T.
タイトル Multiple ERK substrates execute single biological processes in Caenorhabditis elegans germ-line development.
ジャーナル Proc Natl Acad Sci U S A
Abstract RAS-extracellular signal regulated kinase (ERK) signaling governs multiple aspects of cell fate specification, cellular transitions, and growth by regulating downstream substrates through phosphorylation. Understanding how perturbations to the ERK signaling pathway lead to developmental disorders and cancer hinges critically on identification of the substrates. Yet, only a limited number of substrates have been identified that function in vivo to execute ERK-regulated processes. The Caenorhabditis elegans germ line utilizes the well-conserved RAS-ERK signaling pathway in multiple different contexts. Here, we present an integrated functional genomic approach that identified 30 ERK substrates, each of which functions to regulate one or more of seven distinct biological processes during C. elegans germ-line development. Our results provide evidence for three themes that underlie the robustness and specificity of biological outcomes controlled by ERK signaling in C. elegans that are likely relevant to ERK signaling in other organisms: (i) multiple diverse ERK substrates function to control each individual biological process; (ii) different combinations of substrates function to control distinct biological processes; and (iii) regulatory feedback loops between ERK and its substrates help reinforce or attenuate ERK activation. Substrates identified here have conserved orthologs in humans, suggesting that insights from these studies will contribute to our understanding of human diseases involving deregulated ERK activity.
巻・号 106(12)
ページ 4776-81
公開日 2009-3-24
DOI 10.1073/pnas.0812285106
PII 0812285106
PMID 19264959
PMC PMC2660749
MeSH Amino Acid Sequence Animals Caenorhabditis elegans / embryology* Caenorhabditis elegans / enzymology* Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / metabolism Computational Biology Enzyme Activation Extracellular Signal-Regulated MAP Kinases / metabolism* Feedback, Physiological Germ Cells / enzymology* Glycogen Synthase Kinase 3 / chemistry Glycogen Synthase Kinase 3 / metabolism MAP Kinase Signaling System Mammals / metabolism Mitogen-Activated Protein Kinase 1 / chemistry Mitogen-Activated Protein Kinase 1 / metabolism Molecular Sequence Data Phosphorylation Substrate Specificity
IF 9.412
引用数 76
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
線虫 tm1580 tm659 tm544 tm574 tm1743