Recruitment of phosphoinositide 3-kinase defines a positive contribution of tyrosine kinase signaling to E-cadherin function

Jian-Hong Pang, Astrid Kraemer, Samantha J Stehbens, Margaret C Frame, Alpha S Yap

Research output: Contribution to journalArticlepeer-review

Abstract

Classical cadherin adhesion molecules can function as adhesion-activated cell-signaling receptors. One key target for cadherin signaling is the lipid kinase phosphoinositide (PI) 3-kinase, which is recruited to cell-cell contacts and activated by E-cadherin. In this study, we sought to identify upstream factors necessary for E-cadherin to activate PI 3-kinase signaling. We found that inhibition of tyrosine kinase signaling blocked recruitment of PI 3-kinase to E-cadherin contacts and abolished the ability of E-cadherin to activate PI 3-kinase signaling. Tyrosine kinase inhibitors further perturbed several parameters of cadherin function, including cell adhesion and the ability of cells to productively extend nascent cadherin-adhesive contacts. Notably, the functional effects of tyrosine kinase blockade were rescued by expression of a constitutively active form of PI 3-kinase that restores PI 3-kinase signaling. Finally, using dominant negative Src mutants and Src-null cells, we identified Src as one key upstream kinase in the E-cadherin/PI 3-kinase-signaling pathway. Taken together, our findings indicate that tyrosine kinase activity, notably Src signaling, can contribute positively to cadherin function by supporting E-cadherin signaling to PI 3-kinase.
Original languageEnglish
Pages (from-to)3043-50
Number of pages8
JournalJournal of Biological Chemistry
Volume280
Issue number4
DOIs
Publication statusPublished - 28 Jan 2005

Keywords

  • Animals
  • CHO Cells
  • Cadherins
  • Cricetinae
  • Enzyme Activation
  • Genes, Dominant
  • Immunoblotting
  • Immunoprecipitation
  • Microscopy, Fluorescence
  • Mutation
  • Phosphatidylinositol 3-Kinases
  • Plasmids
  • Protein Binding
  • Protein-Serine-Threonine Kinases
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-akt
  • Signal Transduction
  • Time Factors
  • Tyrosine

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