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J. Biol. Chem., Vol. 279, Issue 8, 7082-7090, February 20, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/8/7082    most recent M311581200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kim, S.-M. Articles by Song, W. K. Search for Related Content PubMed PubMed Citation Articles by Kim, S.-M. Articles by Song, W. K. Social Bookmarking                      What's this?

Modulation of Thr Phosphorylation of Integrin ₁ during Muscle Differentiation^*

Seon-Myung Kim, Min Seong Kwon, Chun Shik Park, Kyeong-Rock Choi, Jang-Soo Chun, Joohong Ahn, and Woo Keun Song¶

From the Department of Life Science, Kwangju Institute of Science and Technology, Kwangju 500-712, Korea

By using transient elevations of cytosolic free calcium levels triggered by integrin antibody or laminin (Kwon, M. S., Park, C. S., Choi, K., Park, C.-S., Ahnn, J., Kim, J. I., Eom, S. H., Kaufman, S. J., and Song, W. K. (2000) Mol. Biol. Cell 11, 1433-1443), we have demonstrated that protein phosphatase 2A (PP2A) is implicated in the regulation of reversible phosphorylation of integrin. In E63 skeletal myoblasts, the treatment of PP2A inhibitors such as okadaic acid and endothall induces an increase of phosphorylation of integrin _1A and thereby inhibits integrin-induced elevation of cytosolic calcium level and formation of focal adhesions. None of these effects were in differentiated myotubes expressing the alternate _1D isoform. In the presence of okadaic acid, PP2A in association with integrin _1A was reduced on myoblasts, whereas _1D on myotubes remained bound with PP2A. Both co-immunoprecipitation and in vitro phosphatase assays revealed that dephosphorylation of residues Thr⁷⁸⁸-Thr⁷⁸⁹ in the integrin _1A cytoplasmic domain is dependent upon PP2A activity. Mutational analysis of the cytoplasmic domain and confocal microscopy experiments indicated that substitution of Thr⁷⁸⁸-Thr⁷⁸⁹ with Asn⁷⁸⁸—Asn⁷⁸⁹ is of critical importance for regulating the function of integrin ₁. These results suggest that PP2A may be a primary regulator of threonine phosphorylation of integrin _1A and subsequent activation of downstream signaling molecules. Taken together, we propose that dephosphorylation of residues Thr⁷⁸⁸-Thr⁷⁸⁹ in the cytoplasmic domain of integrin _1A may contribute to the linkage of integrins to focal adhesion sites and induce the association with cytoskeleton proteins. The switch of integrin _1A to _1D isoform in myotubes therefore may be a mechanism to escape from phospho-regulation by PP2A and promotes a more stable association of the cytoskeleton with the extracellular matrix.

Received for publication, October 22, 2003

^* This study was supported in part by grants from National Research Laboratory (The Ministry of Science and Technology). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

These authors contributed equally to this work.

Supported by Brain Korea 21 Program.

^¶ To whom correspondence should be addressed: Dept. of Life Science, Kwangju Institute of Science and Technology, 1 Oryong-dong, Buk-gu, Kwangju 500-712, Korea. Tel.: 82-62-970-2487; Fax: 82-62-970-2484; E-mail: wksong{at}kjist.ac.kr.

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