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Src kinase expression, phosphorylation and activation in human and bovine left ventricles
Author(s) -
Goldman Todd L,
Du Yanmei,
Buttrick Peter M,
Walker Lori A
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.524.7
Subject(s) - proto oncogene tyrosine protein kinase src , tyrosine protein kinase csk , phosphorylation , tyrosine kinase , signal transduction , microbiology and biotechnology , tyrosine phosphorylation , downregulation and upregulation , biology , tyrosine , kinase , chemistry , sh3 domain , biochemistry , gene
Several biochemical signaling pathways contribute to heart failure. Using protein microarrays, we previously identified proteins differentially expressed in human and bovine models of heart failure. One protein upregulated in failing left ventricles (LVs) was CSK (C‐terminal Src kinase), a tyrosine kinase that negatively regulates c‐Src. It has been suggested that Src is important in Ang‐II‐induced signal transduction; that myocardial ischemia may activate Src; and that Src signaling is involved in cardiac hypertrophy. Therefore, we examined the role Src plays in failing LVs. Studies showed that when compared to controls, Src was markedly upregulated in failing LVs, and that another smaller protein product immunologically bound Src antibody. This doublet was isolated using 2‐D gels, and sent to Mass spec for identification. To measure Src phosphorylation, we used phosphospecific antibodies to the Src tyrosine 527 site (negatively regulates Src) and tyrosine 416 site (upregulates Src). Data showed failing samples were not phosphorylated at the Tyr 527 site compared to control. Finally, using a Src kinase activity assay we showed greater Src activity in failing compared to control LVs. These data show there are significant differences in expression, activation and phosphorylation of Src in failing LVs and suggest that Src may be a nodal upstream regulator of progressive LV dysfunction. NIH grant #RO1HL077195