Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/2104
Type: Artigo de periódico
Title: FERM domain interaction with myosin negatively regulates FAK in cardiomyocyte hypertrophy
Author: Santos, Aline M.
Schechtman, Deborah
Cardoso, Alisson C.
Clemente, Carolina F. M. Z.
Silva, Julio C.
Fioramonte, Mariana
Pereira, Michelle B. M.
Marin, Talita M.
Oliveira, Paulo S. L.
Figueira, Ana Carolina M.
Oliveira, Saulo H. P.
Torriani, Iris L.
Gozzo, Fabio C.
Neto, Jose Xavier
Franchini, Kleber G.
Abstract: Focal adhesion kinase (FAK) regulates cellular processes that affect several aspects of development and disease. The FAK N-terminal FERM (4.1 protein-ezrin-radixin-moesin homology) domain, a compact clover-leaf structure, binds partner proteins and mediates intramolecular regulatory interactions. Combined chemical cross-linking coupled to MS, small-angle X-ray scattering, computational docking and mutational analyses showed that the FAK FERM domain has a molecular cleft (similar to 998 angstrom(2)) that interacts with sarcomeric myosin, resulting in FAK inhibition. Accordingly, mutations in a unique short amino acid sequence of the FERM myosin cleft, FP-1, impaired the interaction with myosin and enhanced FAK activity in cardiomyocytes. An FP-1 decoy peptide selectively inhibited myosin interaction and increased FAK activity, promoting cardiomyocyte hypertrophy through activation of the AKT-mammalian target of rapamycin pathway. Our findings uncover an inhibitory interaction between the FAK FERM domain and sarcomeric myosin that presents potential opportunities to modulate the cardiac hypertrophic response through changes in FAK activity.
Editor: Nature Publishing Group
Rights: fechado
Identifier DOI: 10.1038/nchembio.717
Date Issue: 2012
Appears in Collections:FCM - Artigos e Materiais de Revistas Científicas

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