Tyrosine phosphorylation of beta3 integrin provides a binding site for Pyk2

Integrins expressed on leukocytes possess the ability to maintain themselves in a non-adhesive state, thus preventing unwarranted adhesion and uncontrolled inflammation. Leukocyte adhesion is regulated through the modulation of integrin receptors such as alpha(V)beta(3). Firm adhesion to the extrace...

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Bibliographic Details
Published in:The Journal of biological chemistry 2005-04, Vol.280 (15), p.14556-14562
Main Authors: Butler, Boyd, Blystone, Scott D
Format: Article
Language:English
Subjects:
Actins - metabolism
Binding Sites
Cell Adhesion
Cytoplasm - metabolism
Cytoskeleton - metabolism
Extracellular Matrix - metabolism
Focal Adhesion Kinase 2
Glutathione Transferase - metabolism
Humans
Immunoblotting
Immunoprecipitation
Integrin alphaVbeta3 - metabolism
Integrin beta3 - metabolism
K562 Cells
Peptides - chemistry
Phosphorylation
Protein Binding
Protein-Tyrosine Kinases - chemistry
Signal Transduction
Time Factors
Transfection
Tyrosine - chemistry
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Summary:Integrins expressed on leukocytes possess the ability to maintain themselves in a non-adhesive state, thus preventing unwarranted adhesion and uncontrolled inflammation. Leukocyte adhesion is regulated through the modulation of integrin receptors such as alpha(V)beta(3). Firm adhesion to the extracellular matrix and directed cellular motility requires the reorganization of the actin cytoskeleton. The ability of beta(3) to recruit signaling and scaffolding molecules to propagate alpha(V)beta(3) -mediated signals is regulated in part by the phosphorylation of the beta(3) cytoplasmic tail. The identities of integrin-associated signaling molecules within alpha(V)beta(3) podosomes and in particular the proximal binding partners of the beta(3) cytoplasmic tail are not completely known. Here we show that alpha(V)beta(3) ligation induces Pyk2-Tyr-402 phosphorylation and its association with the beta(3) cytoplasmic tail in a beta(3)-Tyr-747 phosphorylation-dependent manner. Pyk2 binding to the beta(3) cytoplasmic tail is direct and dependent upon Pyk2-Tyr-402 and beta(3) -Tyr-747 phosphorylations. These data identify Pyk2 as a phosphorylated beta(3) binding partner, providing a potential structural and signaling platform to achieve alpha(V)beta(3) -mediated remodeling of the actin cytoskeleton.
ISSN:0021-9258