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J. Biol. Chem., Vol. 277, Issue 15, 12931-12936, April 12, 2002
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From the 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.
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
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