Open AccessIdentification of pY19‐caveolin‐2 as a positive regulator of insulin‐stimulated actin cytoskeleton‐dependent mitogenesis
Author(s) -
Kwon Hayeong,
Jeong Kyuho,
Pak Yunbae
Publication year - 2009
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2008.00391.x
Subject(s) - mapk/erk pathway , insulin , insulin receptor , microbiology and biotechnology , phosphorylation , biology , caveolin 1 , actin cytoskeleton , tyrosine phosphorylation , cytoskeleton , endocrinology , biochemistry , cell , insulin resistance
Mitogenic regulation by caveolin‐2 in response to insulin was investigated. Insulin triggered phosphorylation of caveolin‐2 on tyrosine 19. Insulin increased the interaction between pY19‐caveolin‐2 and phospho‐ERK, and that interaction was inhibited by a MEK inhibitor U0126. Insulin‐induced interaction of caveolin‐2 with phospho‐ERK was prevented when tyrosine 19 is mutated to alanine. Insulin relocalized phospho‐ERK and pY19‐caveolin‐2 to the nucleus and their nuclear co‐localization was impaired by U0126. Down‐regulation of caveolin‐2 by caveolin‐2 siRNA arrested the insulin‐induced nuclear localization of ERK with no change in the insulin‐stimulated ERK activation. Of consequence, the caveolin‐2 siRNA attenuated the ERK‐mediated c‐Jun and cyclinD1 expression and DNA synthesis by insulin. In addition, actin cytoskeleton influenced the nuclear translocation of caveolin‐2‐ERK complex. Collectively, our findings underscore the importance of pY19‐caveolin‐2 with the spatial coordination by insulin in ERK‐mediated mitogenic regulation of insulin signalling and indicate that the phosphorylation of pY19‐caveolin‐2 is required for actin cytoskeleton‐dependent ERK nuclear import.