Inducible Tyrosine Phosphorylation of the β3 Integrin Requires the αv Integrin Cytoplasmic Tail*
- Scott D. Blystoneद,
- Frederik P. Lindberg‡§,
- Matthew P. Williams‡,
- Kevin P. McHugh∥** and
- Eric J. Brown‡‡‡
- From the ‡ Department of Medicine, Infectious Diseases Division and the
- ∥ Department of Pathology, Washington University School of Medicine, St. Louis, Missouri, 63110
- ‡‡ To whom correspondence should be addressed: Infectious Diseases, Campus Box 8051, Washington University School of Medicine, St. Louis, MO 63110. Tel.: 314-362-2125; Fax: 314-362-9230; E-mail: ebrown{at}id.wustl.edu.
Abstract
We have found that the integrin β3 chain can be phosphorylated on tyrosine residues in K562 cells transfected with αvβ3. Tyrosine phosphorylation of the β3 cytoplasmic tail is induced by adhesion to αvβ3-specific ligand or antibody or by incubation in manganese-containing buffer. Under the same conditions, β5 does not become tyrosine-phosphorylated in K562 transfected with αvβ5. Phosphorylation of the β3 subunit requires the simultaneous presence of the αv subunit cytoplasmic tail, because neither the αIIb subunit nor a truncated αv subunit is sufficient to permit phosphorylation of β3 when coexpressed as a heterodimer with β3. Finally, tyrosine phosphorylation of the β3 cytoplasmic tail occurs on both human and murine β3 and is inducible in the ovarian carcinoma OV10 as well, independent of expression of integrin-associated protein (CD47). Tyrosine phosphorylation of the β3 integrin subunit facilitates association of Grb-2, an adaptor protein leading to activation of the Ras signaling pathway, and may contribute to the unique functional and signaling capabilities of αvβ3.
Footnotes
-
↵§ Investigators of the Arthritis Foundation.
-
↵¶ Recipient of National Research Service Award Grant AI08990-02 and a grant from the Lucille P. Markey Foundation.
-
↵** Recipient of a National Research Service Award Grant AR08335-02.
-
↵* This work was supported by Grants AI24674 and GM38330 from the National Institutes of Health (to E. J. B.). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
↵1 The abbreviations used are:
- CT
-
cytoplasmic tail
- EGF
-
epidermal growth factor
- mAb
-
monoclonal antibody(ies)
- IAP
-
integrin-associated protein
- PAGE
-
polyacrylamide gel electrophoresis
- PY
-
tyrosinephosphorylated.
-
↵2 K. P. McHugh, S. L. Teitelbaum, and F. P. Ross, manuscript in preparation.
-
- Received June 13, 1996.
- Revision received September 26, 1996.
- © 1996 by The American Society for Biochemistry and Molecular Biology, Inc.
