Protein partners in the life history of activated fibroblast growth factor receptors

A Vecchione, Helen Cooper, Kimberley Hight, Shiva Akbarzadeh, John Heath, Lee Wheldon

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Fibroblast growth factor receptors (FGFRs) are a family of four transmembrane (TM) receptor tyrosine kinases (RTKs) which bind to a large family of fibroblast growth factor (FGF) ligands with varying affinity and specificity. FGFR signaling regulates many physiological and pathological processes in development and tissue homeostasis. Understanding FGFR signaling processes requires the identification of partner proteins which regulate receptor function and biological outputs. In this study, we employ an epitope-tagged, covalently dimerized, and constitutively activated form of FGFR1 to identify potential protein partners by MS. By this approach, we sample candidate FGFR effectors throughout the life history of the receptor. Functional classification of the partners identified revealed specific subclasses involved in protein biosynthesis and folding; structural and regulatory components of the cytoskeleton; known signaling effectors and small GTPases implicated in endocytosis and vesicular trafficking. The kinase dependency of the interaction was determined for a subset of previously unrecognized partners by coimmunoprecipitation, Western blotting, and immunocytochemistry. From this group, the small GTPase Rab5 was selected for functional interrogation. We show that short hairpin (sh) RNA-mediated depletion of Rab5 attenuates the activation of the extracellular-regulated kinase (ERK) 1/2 pathway by FGFR signaling. The strategic approach adopted in this study has revealed bona fide novel effectors of the FGFR signaling pathway.
Original languageEnglish
Pages (from-to)4565-4578
Number of pages14
JournalProteomics
Volume7
Issue number24
Early online date19 Nov 2007
DOIs
Publication statusPublished - 1 Dec 2007

Keywords

  • kinase
  • signaling
  • mass spectrometry
  • FGFR
  • Rab5

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