Calpain Cleavage of the Cytoplasmic Domain of the Integrin 
Subunit (*)
- Xiaoping Du(§)(1)(¶),
- Takaomi C. Saido(§)(2),
- Satoshi Tsubuki(2),
- Fred E. Indig(1),
- Michael J. Williams(1)(**) and
- Mark H. Ginsberg(1)
- From the (1) Department of Vascular Biology, Scripps Research Institute, La Jolla, California 92037 and
- the (2) Department of Molecular Biology, Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, Japan
- ¶ To whom correspondence should be addressed: Dept. of Vascular Biology, Scripps Research Inst., 10666 N. Torrey Pines Rd., La Jolla, CA 92037. Tel.: 619-554-7139; Fax: 619-554-6403.
Abstract
The cytoplasmic domains of integrin β subunits are involved in bidirectional transmembrane signaling. We report that the cytoplasmic
domain of the integrin β
subunit undergoes limited proteolysis by calpain, an intracellular calcium-dependent protease. Calpain cleavage occurs during
platelet aggregation induced by agonists such as thrombin. Five cleavage sites have been identified. Four of these sites (C-terminal
to Thr
, Tyr
, Phe
, and Tyr
) are utilized in intact platelets and flank two NXXY motifs (Asn
-Pro-Leu-Tyr
and Asn
-Ile-Thr-Tyr
). The fifth site (Ala
) is accessible to calpain after EDTA treatment of the α
β
heterodimer. The NXXY motif is critical to the bidirectional signaling functions of β
integrins and their association with the cytoskeleton. Thus, calpain cleavage of the β
cytoplasmic domain may provide a means to regulate integrin signaling functions.
Footnotes
-
↵§ Contributed equally to this work.
-
↵** Recipient of an Arthritis Foundation fellowship.
-
↵* This work was supported in part by Grants HL52547, HL48728, and HL31950 from the National Institutes of Health and by Thrombosys Inc. This is Publication 9514-VB from the Scripps Research Institute. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
↵1 The abbreviations used are:
- HPLC
-
high performance liquid chromatography
- PAGE
-
polyacrylamide gel electrophoresis
- PMSF
-
phenylmethylsulfonyl fluoride
- Ab
-
antibody.
-
- Received August 17, 1995.
- © 1995 by The American Society for Biochemistry and Molecular Biology, Inc.
