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Functional analysis of Src homology 3‐encoding exon (exon 2) of p130Cas in primary fibroblasts derived from exon 2‐specific knockout mice
Author(s) -
Tazaki Tatsuya,
Miyazaki Kazuko,
Hiyama Eiso,
Nakamoto Tetsuya,
Sakai Ryuichi,
Yamasaki Norimasa,
Honda Zenichiro,
Noda Masaki,
Miyasaka Nobuyuki,
Sueda Taijiro,
Honda Hiroaki
Publication year - 2008
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2007.01156.x
Subject(s) - proto oncogene tyrosine protein kinase src , focal adhesion , biology , sh3 domain , exon , tyrosine phosphorylation , microbiology and biotechnology , phosphorylation , adapter molecule crk , sh2 domain , signal transducing adaptor protein , fibronectin , tyrosine , tyrosine kinase , signal transduction , genetics , gene , biochemistry , extracellular matrix
p130Cas (Cas, C rk‐ a ssociated s ubstrate) is an adaptor molecule composed of a Src homology 3 (SH3) domain, a substrate domain (SD) and a Src binding domain (SBD). The SH3 domain of Cas associates with focal adhesion kinase (FAK), but its role in cellular function has not fully been understood. To address this issue, we established and analyzed primary fibroblasts derived from mice expressing a truncated Cas lacking exon 2, which encodes the SH3 domain (Cas Δexon 2). In comparison to wild‐type cells, Cas exon 2 Δ/Δ cells showed reduced motility, which could be due to impaired tyrosine‐phosphorylation of FAK and Cas, reduced FAK/Cas/Src/CrkII binding, and also impaired localization of Cas Δexon 2 to focal adhesions on fibronectin. In addition, to analyze downstream signaling pathways regulated by Cas exon 2, we performed microarray analyses. Interestingly, we found that a deficiency of Cas exon 2 up‐regulated expression of CXC Chemokine Receptor‐4 and CC Chemokine Receptor‐5, which may be regulated by IκBα phosphorylation. These results indicate that the SH3‐encoding exon of Cas participates in cell motility, tyrosine‐phosphorylation of FAK and Cas, FAK/Cas/Src/CrkII complex formation, recruitment of Cas to focal adhesions and regulation of cell motility‐associated gene expression in primary fibroblasts.