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RESEARCH COMMUNICATION
1 integrin function requires phosphorylation-independent regulation by cytoplasmic tyrosines
1 Department of Medicine 2 Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
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 
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 1 integrin cytoplasmic tyrosines with alanines, resulting in the loss of all PTB domain interaction, causes complete loss of 1 integrin function in vivo. In contrast, replacement of 1 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.
[Keywords: Integrin; tyrosine phosphorylation; phospho-tyrosine-binding domain; inside-out signaling; outside-in signaling; conditional knock-in]
Received January 9, 2006; revised version accepted February 17, 2006.
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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1 integrins
Genes & Dev. 2006 20: 1057-1060.
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