Requirements for the localization of p130 Cas to Z-lines in cardiac myocytes

• Autorzy: Kovacic-Milivojevic B , Damsky C.C. , Gardner D.G. , Ilic D.
• Języki publikacji: EN

Abstrakty

EN

The vertebrate heart responds to hemodynamic load with the enlargement of postmitotic, terminally differentiated cardiac myocytes. Such hypertrophic changes are characterized by alterations in sarcomeric organization and gene expression. Previously, we established a role for a nonreceptor tyrosine kinase, focal adhesion kinase, in signaling the changes in cytoskeletal organization associated with hypertrophy [1], Here, we report on data supporting a key role for p130Cas in this process. In neonatal cardiac myocytes FAK, Cas and paxillin are located in sarcomeric Z-lines, suggesting that the Z-line is an important signaling locus in these cells. The expression of different Cas mutants results in a nearly complete loss of sarcomeric organization in these myocytes. Moreover, expression of the C-terminal focal adhesion-targeting domain of FAK both disrupted sarcomeric organization and interfered with the localization of endogenous Cas to Z-lines. These findings suggest that the association of FAK and Cas and the preservation of multiple protein-interaction motifs of Cas are required for the correct assembly of sarcomeres in cardiac myocytes.

Słowa kluczowe

EN

cardiac myocyte; gene expression; hypertrophy; adhesion kinase; heart; tyrosine kinase; vertebrate; myocyte; localization; cytoskeletal organization

• Wydawca: -
• Czasopismo: Cellular and Molecular Biology Letters
• Rocznik: 2002
• Tom: 07
• Numer: 2
• Opis fizyczny: p.323-329,fig.

Twórcy

autor

Kovacic-Milivojevic B

• University of California, San Francisco, California 94143, USA

autor

Damsky C.C.

autor

Gardner D.G.

autor

Ilic D.

Bibliografia

• 1. Kovačič-Milivojevič, B., Roediger, F., Almeida, E. A. C., Damsky, C. H., Gardner, D. G. and Ilić, D. Focal adhesion kinase and p130Cas mediate both sarcomeric organization and activation of genes associated with cardiac myocyte hypertrophy. Mol. Biol. Cell. 12 (2001). 2290-2307.
• 2. Nakamoto, T., Sakai, R., Honda, H., Ogawa, S., Ueno, H., Suzuki, T., Aizawa, S., Yazaki, Y. and Hirai, H. Requirements for localization of p130cas to focal adhesions. Mol. Cell Biol. 17 (1997) 3884-3897.
• 3. Schlaepfer, D. D., Hauck, C. R. and Sieg, D. J. Signaling through focal adhesion kinase. Prog. Biophys. Mol. Biol. 71 (1999). 435-478. Honda, H., Oda, H., Nakamoto, T., Honda, Z., Sakai, R., Suzuki, T., Saito, T., Nakamura, K., Nakao, K., Ishikawa, T., Katsuki, M., Yazaki, Y. and Hirai, H. Cardiovascular anomaly, impaired actin bundling and resistance to Src-induced transformation in mice lacking p130Cas. Nat. Genet. 19 (1998). 361-365.