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Originally published In Press as doi:10.1074/jbc.M110795200 on January 25, 2002

J. Biol. Chem., Vol. 277, Issue 15, 12931-12936, April 12, 2002
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STAT3 Deficiency in Keratinocytes Leads to Compromised Cell Migration through Hyperphosphorylation of p130cas*

Masahiro KiraDagger , Shigetoshi SanoDagger , Satoshi TakagiDagger , Kunihiko YoshikawaDagger , Junji Takeda§, and Satoshi ItamiDagger

From the Dagger  Department of Dermatology, Course of Molecular Medicine, and the § Department of Social and Environmental Medicine, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan

We previously reported that STAT3 plays a crucial role in transducing a signal for migration of keratinocytes (Sano, S., Itami, S., Takeda, K., Tarutani, M., Yamaguchi, Y., Miura, H., Yoshikawa, K., Akira, S., and Takeda, J. (1999) EMBO J. 18, 4657-4668). To clarify the role of STAT3 in signaling the migration, we studied the intracellular signaling pathway through an integrin receptor in STAT3-deficient keratinocytes. STAT3-deficient keratinocytes demonstrated increased adhesiveness and fast spreading on a collagen matrix. Staining with anti-phosphotyrosine antibody revealed that STAT3-deficient keratinocytes had an increased number of tyrosyl-hyperphosphorylated focal adhesions. Analyses with immunoprecipitation revealed that p130cas was constitutively hyperphosphorylated on tyrosine residues, while other focal adhesion molecules such as focal adhesion kinase and paxillin were not. Transfection of STAT3-deficient keratinocytes with an adenoviral vector encoding the wild-type Stat3 gene reversed not only impaired migration but also the increased tyrosine phosphorylation of p130cas. These results strongly suggest that STAT3 in keratinocytes plays a critical role in turnover of tyrosine phosphorylation of p130cas, modulating cell adhesiveness to the substratum leading to growth factor-dependent cell migration.


* This work was supported by grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.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.

To whom correspondence should be addressed: Dept. of Dermatology, Course of Molecular Medicine, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita 565-0871, Japan. Tel.: 81-6-6879-3031; Fax: 81-6-6879-3039; E-mail: itami@derma.med.osaka-u.ac.jp.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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