{'fraction_non_alphanumeric': 0.04103671706263499, 'fraction_numerical': 0.03959683225341973, 'mean_word_length': 6.277486910994765, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
LPS‐induced post‐translational modifications of hsp90 in pulmonary endothelial cells

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 pp60src inhibitor, PP2 (10μM). Infection of BPAE with adenoviral constructs of constitutively active pp60src, but not of wild type or dominant negative pp60src, 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, pp60src activation (Y418 phosphorylation) in BPAEs was also PP2‐ and 17‐AAG‐ sensitive. We conclude that LPS activates hsp90 via pp60src‐ and 17‐AAG‐ sensitive tyrosine phosphorylation.