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Genes & Dev. 20 (8): 927-932

Copyright © 2006 by Cold Spring Harbor Laboratory Press.

RESEARCH COMMUNICATION

In vivo beta1 integrin function requires phosphorylation-independent regulation by cytoplasmic tyrosines

Hong Chen1, Zhiying Zou1, Kendra L. Sarratt2, Diane Zhou1, MaoZhen Zhang1, Eric Sebzda1, Daniel A. Hammer2, and Mark L. Kahn1,3

1 Department of Medicine
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 beta 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 beta1 integrin cytoplasmic tyrosines with alanines, resulting in the loss of all PTB domain interaction, causes complete loss of beta1 integrin function in vivo. In contrast, replacement of beta1 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.

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

Received for publication January 9, 2006. Accepted for publication February 17, 2006.

3 Corresponding author.

E-MAIL markkahn{at}mail.med.upenn.edu; FAX (215) 573-2094.

Supplemental material is available at http://www.genesdev.org.

Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1408306

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