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In vivo β1 integrin function requires phosphorylation-independent regulation by cytoplasmic tyrosines

Genes & Dev., 15 April 2006
Vol. 20, Issue 8, p. 927-932
DOI: 10.1101/gad.1408306

In vivo β1 integrin function requires phosphorylation-independent regulation by cytoplasmic tyrosines

  1. Hong Chen1,
  2. Zhiying Zou1,
  3. Kendra L. Sarratt2,
  4. Diane Zhou1,
  5. MaoZhen Zhang1,
  6. Eric Sebzda1,
  7. Daniel A. Hammer2, and
  8. Mark L. Kahn1,3
  1. 1 Department of Medicine
  2. 2 Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA

Abstract

Integrins are heterodimeric adhesion receptors associated with bidirectional signaling. In vitro studies support a role for the binding of evolutionarily conserved tyrosine motifs (NPxY) in the β integrin cytoplasmic tail to phosphotyrosine-binding (PTB) domain-containing proteins, an interaction proposed to be dynamically regulated by tyrosine phosphorylation. Here we show that replacement of both β1 integrin cytoplasmic tyrosines with alanines, resulting in the loss of all PTB domain interaction, causes complete loss of β1 integrin function in vivo. In contrast, replacement of β1 integrin cytoplasmic tyrosines with phenylalanines, a mutation that prevents tyrosine phosphorylation, conserves in vivo integrin function. These results have important implications for the molecular mechanism and regulation of integrin function.

  • Integrin
  • tyrosine phosphorylation
  • phospho-tyrosine-binding domain
  • inside-out signaling
  • outside-in signaling
  • conditional knock-in

Footnotes

Citation:

H. Chen, Z. Zou, K. L. Sarratt, D. Zhou, M. Zhang, E. Sebzda, D. A. Hammer, and M. L. Kahn, In vivo β1 integrin function requires phosphorylation-independent regulation by cytoplasmic tyrosines. Genes & Dev. 20, 927-932 (2006).

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