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Nodal points and complexity of Notch-Ras signal integration.
Hurlbut, Gregory D; Kankel, Mark W; Artavanis-Tsakonas, Spyros.
Affiliation
  • Hurlbut GD; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A ; 106(7): 2218-23, 2009 Feb 17.
Article in En | MEDLINE | ID: mdl-19171888
Metazoans use a handful of highly conserved signaling pathways to create a signaling backbone that governs development. How these few signals have such a versatile action likely depends upon the larger-scale network they form through integration, as exemplified by cross-talk between the Notch and receptor tyrosine kinase (RTK) pathways. We examined the transcriptional output of Notch-RTK cross-talk during Drosophila development and present in vivo data supporting a role for selected mutually regulated genes in signal integration. Interestingly, Notch-RTK integration did not lead to general antagonism of either pathway, as is commonly believed. Instead, integration had a combinatorial effect on specific cross-regulated targets, which unexpectedly included numerous core components of the RTK and other major signaling pathways (TGF-beta, Hh, Jak/Stat, nuclear receptor and Wnt). We find the majority of Ras-responsive genes are also Notch-responsive, suggesting Notch may function to specify the response to Ras activation.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Gene Expression Regulation / Receptor Protein-Tyrosine Kinases / Ras Proteins / Receptors, Notch Type of study: Prognostic_studies Limits: Animals Language: En Journal: Proc Natl Acad Sci U S A Year: 2009 Document type: Article Affiliation country: Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Gene Expression Regulation / Receptor Protein-Tyrosine Kinases / Ras Proteins / Receptors, Notch Type of study: Prognostic_studies Limits: Animals Language: En Journal: Proc Natl Acad Sci U S A Year: 2009 Document type: Article Affiliation country: Country of publication: