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.
机构:
UNIV N CAROLINA, LINEBERGER COMPREHENS CANC CTR, CHAPEL HILL, NC 27599 USAUNIV N CAROLINA, LINEBERGER COMPREHENS CANC CTR, CHAPEL HILL, NC 27599 USA
Burridge, K
ChrzanowskaWodnicka, M
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UNIV N CAROLINA, LINEBERGER COMPREHENS CANC CTR, CHAPEL HILL, NC 27599 USAUNIV N CAROLINA, LINEBERGER COMPREHENS CANC CTR, CHAPEL HILL, NC 27599 USA
机构:
Childrens Hosp Los Angeles, Dept Pathol, Sect Mol Carcinogenesis, Los Angeles, CA 90027 USAChildrens Hosp Los Angeles, Dept Pathol, Sect Mol Carcinogenesis, Los Angeles, CA 90027 USA
de Jong, R
van Wijk, A
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Childrens Hosp Los Angeles, Dept Pathol, Sect Mol Carcinogenesis, Los Angeles, CA 90027 USAChildrens Hosp Los Angeles, Dept Pathol, Sect Mol Carcinogenesis, Los Angeles, CA 90027 USA
van Wijk, A
Haataja, L
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机构:
Childrens Hosp Los Angeles, Dept Pathol, Sect Mol Carcinogenesis, Los Angeles, CA 90027 USAChildrens Hosp Los Angeles, Dept Pathol, Sect Mol Carcinogenesis, Los Angeles, CA 90027 USA
Haataja, L
Heisterkamp, N
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h-index: 0
机构:
Childrens Hosp Los Angeles, Dept Pathol, Sect Mol Carcinogenesis, Los Angeles, CA 90027 USAChildrens Hosp Los Angeles, Dept Pathol, Sect Mol Carcinogenesis, Los Angeles, CA 90027 USA
Heisterkamp, N
Groffen, J
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h-index: 0
机构:
Childrens Hosp Los Angeles, Dept Pathol, Sect Mol Carcinogenesis, Los Angeles, CA 90027 USAChildrens Hosp Los Angeles, Dept Pathol, Sect Mol Carcinogenesis, Los Angeles, CA 90027 USA
机构:
UNIV N CAROLINA, LINEBERGER COMPREHENS CANC CTR, CHAPEL HILL, NC 27599 USAUNIV N CAROLINA, LINEBERGER COMPREHENS CANC CTR, CHAPEL HILL, NC 27599 USA
Burridge, K
ChrzanowskaWodnicka, M
论文数: 0引用数: 0
h-index: 0
机构:
UNIV N CAROLINA, LINEBERGER COMPREHENS CANC CTR, CHAPEL HILL, NC 27599 USAUNIV N CAROLINA, LINEBERGER COMPREHENS CANC CTR, CHAPEL HILL, NC 27599 USA
机构:
Childrens Hosp Los Angeles, Dept Pathol, Sect Mol Carcinogenesis, Los Angeles, CA 90027 USAChildrens Hosp Los Angeles, Dept Pathol, Sect Mol Carcinogenesis, Los Angeles, CA 90027 USA
de Jong, R
van Wijk, A
论文数: 0引用数: 0
h-index: 0
机构:
Childrens Hosp Los Angeles, Dept Pathol, Sect Mol Carcinogenesis, Los Angeles, CA 90027 USAChildrens Hosp Los Angeles, Dept Pathol, Sect Mol Carcinogenesis, Los Angeles, CA 90027 USA
van Wijk, A
Haataja, L
论文数: 0引用数: 0
h-index: 0
机构:
Childrens Hosp Los Angeles, Dept Pathol, Sect Mol Carcinogenesis, Los Angeles, CA 90027 USAChildrens Hosp Los Angeles, Dept Pathol, Sect Mol Carcinogenesis, Los Angeles, CA 90027 USA
Haataja, L
Heisterkamp, N
论文数: 0引用数: 0
h-index: 0
机构:
Childrens Hosp Los Angeles, Dept Pathol, Sect Mol Carcinogenesis, Los Angeles, CA 90027 USAChildrens Hosp Los Angeles, Dept Pathol, Sect Mol Carcinogenesis, Los Angeles, CA 90027 USA
Heisterkamp, N
Groffen, J
论文数: 0引用数: 0
h-index: 0
机构:
Childrens Hosp Los Angeles, Dept Pathol, Sect Mol Carcinogenesis, Los Angeles, CA 90027 USAChildrens Hosp Los Angeles, Dept Pathol, Sect Mol Carcinogenesis, Los Angeles, CA 90027 USA