Binding of paxillin to α4 integrins modifies integrin-dependent biological responses

Shouchun Liu, Sheila M. Thomas, Darren G. Woodside, David M. Rose, William B. Kiosses, Martin Pfaff and Mark H. Ginsberg ()
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Shouchun Liu: VB-2, The Scripps Research Institute
Sheila M. Thomas: Cancer Biology Program, Beth Israel Deaconess Medical Center and Harvard Medical School
Darren G. Woodside: VB-2, The Scripps Research Institute
David M. Rose: VB-2, The Scripps Research Institute
William B. Kiosses: VB-2, The Scripps Research Institute
Martin Pfaff: Ecole Normale Superieure de Lyon
Mark H. Ginsberg: VB-2, The Scripps Research Institute

Nature, 1999, vol. 402, issue 6762, 676-681

Abstract: Abstract The α4 integrins are indispensable for embryogenesis, haematopoiesis and immune responses1,2, possibly because α4 regulates cellular functions differently from other integrins through its cytoplasmic tail3. We used novel mimics4 of the α4 tail to identify molecules that could account for α4-specific signalling. Here we report that the α4 tail, but not several other α-subunit tails, binds tightly to the signalling adaptor paxillin. Paxillin physically associated with α4 integrins in Jurkat T cells at high stoichiometry, and joining the α4 tail to αIIb resulted in a complex of integrin αIIbβ3 with paxillin. This association markedly enhanced the rates of αIIbβ3-dependent phosphorylation of focal adhesion kinase and cell migration. It also reduced cell spreading, focal adhesion and stress fibre formation. A point mutation within the α4 tail that disrupts paxillin binding reversed all of these effects. Furthermore, α4β1-dependent adhesion to VCAM-1 led to spreading of mouse embryonic fibroblasts derived from paxillin-null but not from wild-type mice. Thus, the tight association of paxillin with the α4 tail leads to distinct biochemical and biological responses to integrin-mediated cell adhesion.

Date: 1999
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DOI: 10.1038/45264

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