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 |