Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/194592
Type: Artigo de periódico
Title: Early Activation Of The Multicomponent Signaling Complex Associated With Focal Adhesion Kinase Induced By Pressure Overload In The Rat Heart.
Author: Franchini, K G
Torsoni, A S
Soares, P H
Saad, M J
Abstract: Mechanical overload elicits functional and structural adaptive mechanisms in cardiac muscle. Signaling pathways linked to integrin/cytoskeleton complexes may have a function in mediation of the effects of mechanical stimulus in myocardial cells. We investigated the tyrosine phosphorylation and the assembly of the multicomponent signaling complex associated with focal adhesion kinase (Fak) and the actin cytoskeleton in the overloaded myocardium of rats. Pressure overload induced a 3-fold increase in Fak tyrosine phosphorylation within 3 minutes after a 60-mm Hg rise in aortic pressure. A pressure stimulus that lasted for 60 minutes was accompanied by a 5-fold increase in the amount of tyrosine-phosphorylated Fak, and a stimulus as low as 10 mm Hg doubled the amount of tyrosine-phosphorylated Fak in the myocardium within 10 minutes. Pressure overload also induced a time-dependent association of actin with Fak and an increase in the amount of Fak detected in the cytoskeletal fraction of the myocardium. These events were paralleled by c-Src activation and binding to Fak and by an association of Grb2 and p85 subunit of phosphatidylinositol 3-kinase with Fak. Erk1/2 and Akt, two possible downstream effectors of Fak via Grb2 and phosphatidylinositol 3-kinase, were also shown to be activated in parallel with Fak. These findings show that pressure overload induced a rapid activation of the Fak multiple signaling complex in the myocardium of rats, which suggests that this mechanism may have a role in mechanotransduction in the myocardium.
Subject: Adaptor Proteins, Signal Transducing
Animals
Aorta
Blood Pressure
Enzyme Activation
Focal Adhesion Kinase 1
Focal Adhesion Protein-tyrosine Kinases
Grb2 Adaptor Protein
Male
Mitogen-activated Protein Kinase 1
Mitogen-activated Protein Kinase 3
Mitogen-activated Protein Kinases
Myocardium
Phosphatidylinositol 3-kinases
Phosphorylation
Pressure
Protein-serine-threonine Kinases
Protein-tyrosine Kinases
Proteins
Proto-oncogene Proteins
Proto-oncogene Proteins C-akt
Proto-oncogene Proteins Pp60(c-src)
Rats
Rats, Wistar
Signal Transduction
Tissue Distribution
Tyrosine
Rights: fechado
Identifier DOI: 
Address: http://www.ncbi.nlm.nih.gov/pubmed/11009560
Date Issue: 2000
Appears in Collections:Unicamp - Artigos e Outros Documentos

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