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      A module of negative feedback regulators defines growth factor signaling.

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          Abstract

          Signaling pathways invoke interplays between forward signaling and feedback to drive robust cellular response. In this study, we address the dynamics of growth factor signaling through profiling of protein phosphorylation and gene expression, demonstrating the presence of a kinetically defined cluster of delayed early genes that function to attenuate the early events of growth factor signaling. Using epidermal growth factor receptor signaling as the major model system and concentrating on regulation of transcription and mRNA stability, we demonstrate that a number of genes within the delayed early gene cluster function as feedback regulators of immediate early genes. Consistent with their role in negative regulation of cell signaling, genes within this cluster are downregulated in diverse tumor types, in correlation with clinical outcome. More generally, our study proposes a mechanistic description of the cellular response to growth factors by defining architectural motifs that underlie the function of signaling networks.

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          Author and article information

          Journal
          Nat Genet
          Nature genetics
          Springer Science and Business Media LLC
          1061-4036
          1061-4036
          Apr 2007
          : 39
          : 4
          Affiliations
          [1 ] Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel.
          Article
          ng1987
          10.1038/ng1987
          17322878
          a134a4c9-bc69-470a-b130-83b22fb8f6d3

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