Integrin activation and focal complex formation in cardiac hypertrophy

Citation
M. Laser et al., Integrin activation and focal complex formation in cardiac hypertrophy, J BIOL CHEM, 275(45), 2000, pp. 35624-35630
Citations number
59
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
00219258 → ACNP
Volume
275
Issue
45
Year of publication
2000
Pages
35624 - 35630
Database
ISI
SICI code
0021-9258(20001110)275:45<35624:IAAFCF>2.0.ZU;2-J
Abstract
Cardiac hypertrophy is characterized by both remodeling of the extracellula r matrix (ECM) and hypertrophic growth of the cardiocytes. Here we show inc reased expression and cytoskeletal association of the ECM: proteins fibrone ctin and vitronectin in pressure-overloaded feline myocardium. These change s are accompanied by cytoskeletal binding and phosphorylation of focal adhe sion kinase (FAK) at Tyr-397 and Tyr-925, c-Src at Tyr-416, recruitment of the adapter proteins p130(Cas), Shc, and Nck, and activation of the extrace llular-regulated: kinases ERK1/2. A synthetic peptide containing the Arg-Gl y-Asp (RGD) motif of fibronectin and vitronectin was used to stimulate adul t feline cardiomyocytes cultured on laminin or within a type-1 collagen mat rix. Whereas cardiocytes under both conditions showed RGD-stimulated ERK1/2 activation, only collagen-embedded cells exhibited cytoskeletal assembly o f FAK, c-Src, Nck, and Shc. In ROD-stimulated collagen-embedded cells, FAK was phosphorylated only at Tyr-397 and; c-Src association occurred without Tyr-416 phosphorylation and p130(Cas) association. Therefore, c-Src activat ion is not required for its cytoskeletal binding:but may be important for a dditional phosphorylation of:FAK. Overall, our study suggests that multiple signaling pathways originate in pressure-overloaded heart following integr in engagement with ECM proteins, including focal complex formation and ERK1 /2 activation, and many of these pathways can be activated in cardiomyocyte s via RGD-stimulated integrin activation.