Synergistic promotion of c-Src activation and cell migration by Cas and AND-34/BCAR3

Rebecca B. Riggins, Lawrence Quilliam, Amy H. Bouton

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

The adapter molecule p130Cas (Cas) plays a role in cellular processes such as proliferation, survival, cell adhesion, and migration. The ability of Cas to promote migration has been shown to be dependent upon its carboxyl terminus, which contains a bipartite binding site for the protein tyrosine kinase c-Src (Src). The association between Src and Cas enhances Src kinase activity, and like Cas, Src plays an important role in cell proliferation and migration. In this study, we show that Src and Cas function cooperatively to promote cell migration in a manner that depends upon kinase-active Src. Another carboxyl-terminal binding partner of Cas, AND-34/BCAR3 (AND-34), functions synergistically with Cas to enhance Src activation and cell migration. The carboxyl-terminal guanine nucleotide exchange factor domain of AND-34, as well as the activity of its putative target Rap1, contribute to these events. A mechanism through which AND-34 may regulate Cas-dependent cell migration is suggested by the finding that Cas becomes redistributed from focal adhesions to lamellipodia located at the leading edge of AND-34 overexpressing cells. These data thus provide insight into how Cas and AND-34 may function together to stimulate Src signaling pathways and promote cell migration.

Original languageEnglish
Pages (from-to)28264-28273
Number of pages10
JournalJournal of Biological Chemistry
Volume278
Issue number30
DOIs
StatePublished - Jul 25 2003

Fingerprint

Guanine Nucleotide Exchange Factors
src-Family Kinases
Cell adhesion
Cell proliferation
Cell Movement
Phosphotransferases
Adhesion
Chemical activation
Binding Sites
Association reactions
Molecules
Pseudopodia
Focal Adhesions
Cell Adhesion
CSK tyrosine-protein kinase
Carrier Proteins
Cell Proliferation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Synergistic promotion of c-Src activation and cell migration by Cas and AND-34/BCAR3. / Riggins, Rebecca B.; Quilliam, Lawrence; Bouton, Amy H.

In: Journal of Biological Chemistry, Vol. 278, No. 30, 25.07.2003, p. 28264-28273.

Research output: Contribution to journalArticle

@article{e2779f650a8947abb7e59519c4370306,
title = "Synergistic promotion of c-Src activation and cell migration by Cas and AND-34/BCAR3",
abstract = "The adapter molecule p130Cas (Cas) plays a role in cellular processes such as proliferation, survival, cell adhesion, and migration. The ability of Cas to promote migration has been shown to be dependent upon its carboxyl terminus, which contains a bipartite binding site for the protein tyrosine kinase c-Src (Src). The association between Src and Cas enhances Src kinase activity, and like Cas, Src plays an important role in cell proliferation and migration. In this study, we show that Src and Cas function cooperatively to promote cell migration in a manner that depends upon kinase-active Src. Another carboxyl-terminal binding partner of Cas, AND-34/BCAR3 (AND-34), functions synergistically with Cas to enhance Src activation and cell migration. The carboxyl-terminal guanine nucleotide exchange factor domain of AND-34, as well as the activity of its putative target Rap1, contribute to these events. A mechanism through which AND-34 may regulate Cas-dependent cell migration is suggested by the finding that Cas becomes redistributed from focal adhesions to lamellipodia located at the leading edge of AND-34 overexpressing cells. These data thus provide insight into how Cas and AND-34 may function together to stimulate Src signaling pathways and promote cell migration.",
author = "Riggins, {Rebecca B.} and Lawrence Quilliam and Bouton, {Amy H.}",
year = "2003",
month = "7",
day = "25",
doi = "10.1074/jbc.M303535200",
language = "English",
volume = "278",
pages = "28264--28273",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "30",

}

TY - JOUR

T1 - Synergistic promotion of c-Src activation and cell migration by Cas and AND-34/BCAR3

AU - Riggins, Rebecca B.

AU - Quilliam, Lawrence

AU - Bouton, Amy H.

PY - 2003/7/25

Y1 - 2003/7/25

N2 - The adapter molecule p130Cas (Cas) plays a role in cellular processes such as proliferation, survival, cell adhesion, and migration. The ability of Cas to promote migration has been shown to be dependent upon its carboxyl terminus, which contains a bipartite binding site for the protein tyrosine kinase c-Src (Src). The association between Src and Cas enhances Src kinase activity, and like Cas, Src plays an important role in cell proliferation and migration. In this study, we show that Src and Cas function cooperatively to promote cell migration in a manner that depends upon kinase-active Src. Another carboxyl-terminal binding partner of Cas, AND-34/BCAR3 (AND-34), functions synergistically with Cas to enhance Src activation and cell migration. The carboxyl-terminal guanine nucleotide exchange factor domain of AND-34, as well as the activity of its putative target Rap1, contribute to these events. A mechanism through which AND-34 may regulate Cas-dependent cell migration is suggested by the finding that Cas becomes redistributed from focal adhesions to lamellipodia located at the leading edge of AND-34 overexpressing cells. These data thus provide insight into how Cas and AND-34 may function together to stimulate Src signaling pathways and promote cell migration.

AB - The adapter molecule p130Cas (Cas) plays a role in cellular processes such as proliferation, survival, cell adhesion, and migration. The ability of Cas to promote migration has been shown to be dependent upon its carboxyl terminus, which contains a bipartite binding site for the protein tyrosine kinase c-Src (Src). The association between Src and Cas enhances Src kinase activity, and like Cas, Src plays an important role in cell proliferation and migration. In this study, we show that Src and Cas function cooperatively to promote cell migration in a manner that depends upon kinase-active Src. Another carboxyl-terminal binding partner of Cas, AND-34/BCAR3 (AND-34), functions synergistically with Cas to enhance Src activation and cell migration. The carboxyl-terminal guanine nucleotide exchange factor domain of AND-34, as well as the activity of its putative target Rap1, contribute to these events. A mechanism through which AND-34 may regulate Cas-dependent cell migration is suggested by the finding that Cas becomes redistributed from focal adhesions to lamellipodia located at the leading edge of AND-34 overexpressing cells. These data thus provide insight into how Cas and AND-34 may function together to stimulate Src signaling pathways and promote cell migration.

UR - http://www.scopus.com/inward/record.url?scp=0041845239&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0041845239&partnerID=8YFLogxK

U2 - 10.1074/jbc.M303535200

DO - 10.1074/jbc.M303535200

M3 - Article

VL - 278

SP - 28264

EP - 28273

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 30

ER -