A molecular mechanism of integrin crosstalk: α(v)β3 Suppression of calcium/calmodulin-dependent protein kinase II regulates α5β1 function

Scott D. Blystone, Suzanne E. Slater, Matthew P. Williams, Michael T. Crow, Eric J. Brown

Research output: Contribution to journalArticlepeer-review


Many cells express more than one integrin receptor for extracellular matrix, and in vivo these receptors may be simultaneously engaged. Ligation of one integrin may influence the behavior of others on the cell, a phenomenon we have called integrin crosstalk. Ligation of the integrin α(v)β3 inhibits both phagocytosis and migration mediated by α5β1 on the same cell, and the β3 cytoplasmic tail is necessary and sufficient for this regulation of α5β1. Ligation of α5β1 activates the calcium- and calmodulin-dependent protein kinase II (CamKII). This activation is required for α5β1-mediated phagocytosis and migration. Simultaneous ligation of α(v)β3 or expression of a chimeric molecule with a free β3 cytoplasmic tail prevents α5β1-mediated activation of CamKII. Expression of a constitutively active CamKII restores a5β1 functions blocked by α(v)β3- initiated integrin crosstalk. Thus, α(v)β3 inhibition of α5β1 activation of CamKII is required for its role in integrin crosstalk. Structure-function analysis of the β3 cytoplasmic tail demonstrates a requirement for Ser752 in β3-mediated suppression of CamKII activation, while crosstalk is independent of Tyr747 and Tyr759, implicating Ser752, but not β3 tyrosine phosphorylation in initiation of the α(v)β3 signal for integrin crosstalk.

Original languageEnglish (US)
Pages (from-to)889-897
Number of pages9
JournalJournal of Cell Biology
Issue number4
StatePublished - May 17 1999


  • Crosstalk signaling
  • Integrin
  • Kinase
  • Vitronectin

ASJC Scopus subject areas

  • Cell Biology


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