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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

alpha B-crystallin interacts with and prevents stress-activated proteolysis of focal adhesion kinase by calpain in cardiomyocytes

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Author(s):
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Pereira, Michelle B. M. [1] ; Santos, Aline M. [1] ; Goncalves, Danieli C. [1] ; Cardoso, Alisson C. [1] ; Consonni, Silvio R. [1] ; Gozzo, Fabio C. [2] ; Oliveira, Paulo S. [1] ; Pereira, Ana Helena M. [1] ; Figueiredo, Alana R. [2] ; Tiroli-Cepeda, Ana O. [2] ; Ramos, Carlos H. I. [2] ; de Thomaz, Andre A. [3] ; Cesar, Carlos L. [3] ; Franchini, Kleber G. [1, 4]
Total Authors: 14
Affiliation:
[1] Ctr Res Energy & Mat, Brazilian Natl Lab Biosci, BR-13084971 Campinas, SP - Brazil
[2] Univ Estadual Campinas, Inst Chem, BR-13083970 Campinas, SP - Brazil
[3] Univ Estadual Campinas, Gleb Wataghin Phys Inst, BR-13083859 Campinas, SP - Brazil
[4] Univ Estadual Campinas, Sch Med, Dept Internal Med, BR-13081970 Campinas, SP - Brazil
Total Affiliations: 4
Document type: Journal article
Source: NATURE COMMUNICATIONS; v. 5, OCT 2014.
Web of Science Citations: 16
Abstract

Focal adhesion kinase (FAK) contributes to cellular homeostasis under stress conditions. Here we show that alpha B-crystallin interacts with and confers protection to FAK against calpain-mediated proteolysis in cardiomyocytes. A hydrophobic patch mapped between helices 1 and 4 of the FAK FAT domain was found to bind to the beta 4-beta 8 groove of alpha B-crystallin. Such an interaction requires FAK tyrosine 925 and is enhanced following its phosphorylation by Src, which occurs upon FAK stimulation. alpha B-crystallin silencing results in calpain-dependent FAK depletion and in the increased apoptosis of cardiomyocytes in response to mechanical stress. FAK overexpression protects cardiomyocytes depleted of alpha B-crystallin against the stretch-induced apoptosis. Consistently, load-induced apoptosis is blunted in the hearts from cardiac-specific FAK transgenic mice transiently depleted of alpha B-crystallin by RNA interference. These studies define a role for alpha B-crystallin in controlling FAK function and cardiomyocyte survival through the prevention of calpain-mediated degradation of FAK. (AU)

FAPESP's process: 06/54878-3 - Pathogenesis of cardiac hypertrophy and failure: mechanisms activated by mechanical stress
Grantee:Kleber Gomes Franchini
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 08/57805-2 - Institute of Bioanalytics
Grantee:Lauro Tatsuo Kubota
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 10/02628-9 - Cross-linking coupled to mass spectrometry: FERM/Miosin complex interaction mapping
Grantee:Mariana Fioramonte
Support Opportunities: Scholarships in Brazil - Master