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LPS‐induced post‐translational modifications of hsp90 in pulmonary endothelial cells
Author(s) -
Handa Vaishali,
Snead Connie,
Black Stephen M,
Catravas John D
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.1024.14
Subject(s) - hsp90 , phosphorylation , heat shock protein , tyrosine phosphorylation , proto oncogene tyrosine protein kinase src , tyrosine , hsp90 inhibitor , chemistry , inflammation , microbiology and biotechnology , cancer research , biology , biochemistry , immunology , gene
Inflammation plays an important role in the pathogenesis of pulmonary vascular diseases. Heat shock protein 90 (hsp90), which accounts for approximately 1 to 2% of total cellular proteins, exists in multi‐protein complexes with various co‐chaperones and client proteins, many of which are crucial to inflammation. Whereas post‐translational modifications affect hsp90 function, there is no information on how inflammation may bring about such modifications. In bovine pulmonary arterial endothelial cells (BPAE), LPS (1000 EU/ml) produced a significant, time‐dependent increase in tyrosine phosphorylation of hsp90, which was prevented by pre‐treatment with the pp60 src inhibitor, PP2 (10μM). Infection of BPAE with adenoviral constructs of constitutively active pp60 src , but not of wild type or dominant negative pp60 src , caused an increase in hsp90 tyrosine phosphorylation of hsp90 which was further augmented by exposure to LPS. Pretreatment (2hr) with the hsp90 inhibitor 17‐(Allylamino)‐17‐demethoxygeldanamycin (17‐AAG; 1μg/ml) significantly suppressed LPS‐mediated hsp90 tyrosine phosphorylation. Furthermore, pp60 src activation (Y418 phosphorylation) in BPAEs was also PP2‐ and 17‐AAG‐ sensitive. We conclude that LPS activates hsp90 via pp60 src ‐ and 17‐AAG‐ sensitive tyrosine phosphorylation.