UNC-51-like kinase regulation of fibroblast growth factor receptor substrate 2/3

Adam W. Avery, Claudia Figueroa, Anne B. Vojtek

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

UNC-51-like kinases (ULK) are members of an evolutionarily conserved sub-family of ubiquitously expressed serine/threonine-specific protein kinases. Here we report that fibroblast growth factor receptor substrate (FRS) 2/3 are novel ULK2 carboxy-terminal domain interacting proteins. FRS2/3 are homologs that function as adaptor proteins to mediate signaling of multiple receptor tyrosine kinases. ULK2 interacts with the phospho-tyrosine binding (PTB) domain of FRS2/3. We demonstrate that siRNA targeting ULK2 in mouse P19 cells results in elevated FGFR1 mediated FRS3 and SHP2 tyrosyl phosphorylation. In addition, RNAi-mediated decrease in ULK2 causes increased interaction between FGFR1 and FRS3. ULK2 phosphorylates FRS2/3 in vitro, suggesting that ULK2 mediated phosphorylation may be a mechanism of FRS2/3 regulation. The data presented support a model in which ULK2, by interaction with FRS2/3 and inhibition of SynGAP, functions to negatively regulate tyrosyl phosphorylation of signaling proteins downstream of FGFR1.

Original languageEnglish (US)
Pages (from-to)177-184
Number of pages8
JournalCellular Signalling
Volume19
Issue number1
DOIs
StatePublished - Jan 2007

Bibliographical note

Funding Information:
We thank Jennifer Taylor for helpful discussions and technical assistance, and E.J. Brace for help with design and construction of SynGAP RNAi expression vectors. We thank Mary E. Hatten (pME18S-3HA-mUnc51.2[wt] and pME18S-3HA-mUnc51.2[kt]), and Christin Carter-Su and Jack Dixon (pCMV5-PTP1D) for expression vectors. We thank Jenn-Yah Yu for cDNA used for FRS3 cloning. This work was supported by the Cellular Biotechnology Training Program at the University of Michigan and by a Research Scholar Grant RSG-01-177-01-MGO from the American Cancer Society.

Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.

Keywords

  • FGFR
  • FRS2
  • FRS2alpha
  • FRS2beta
  • FRS3
  • PTB domain
  • ULK2
  • UNC-51-like kinase

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