Phosphorylation of tyrosine residues 31 and 118 on paxillin regulates cell migration through an association with CRK in NBT-II cells

被引:241
作者
Petit, V
Boyer, B
Lentz, D
Turner, CE
Thiery, JP
Vallés, AM
机构
[1] Inst Curie, Sect Rech, CNRS, UMR 144, F-75248 Paris 05, France
[2] SUNY Syracuse, Hlth Sci Ctr, Dept Anat & Cell Biol, Syracuse, NY 13210 USA
关键词
cell migration; collagen; paxillin; tyrosine phosphorylation; Crk;
D O I
10.1083/jcb.148.5.957
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Identification of signaling molecules that regulate cell migration is important for understanding fundamental processes in development and the origin of various pathological conditions. The migration of Nara Bladder Tumor II (NBT-II) cells was used to determine which signaling molecules are specifically involved in the collagen-mediated locomotion. We show here that paxillin is tyrosine phosphorylated after induction of motility on collagen. Overexpression of paxillin mutants in which tyrosine 31 and/or tyrosine 118 were replaced by phenylalanine effectively impaired cell motility, Moreover, stimulation of motility by collagen preferentially enhanced the association of paxillin with the SH2 domain of the adaptor protein CrkII. Mutations in both tyrosine 31 and 118 diminished the phosphotyrosine content of paxillin and prevented the formation of the paxillin-Crk complex, suggesting that this association is necessary for collagen-mediated NET-II cell migration. Other responses to collagen, such as cell adhesion and spreading, were not affected by these mutations. Overexpression of wild-type paxillin or Crk could bypass the migration-deficient phenotype. Both the SH2 and the SH3 domains of CrkII are shown to play a critical role in this collagen-mediated migration. These results demonstrate the important role of the paxillin-Crk complex in the collagen-induced cell motility.
引用
收藏
页码:957 / 969
页数:13
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