Premium
The full‐length isoform of the mouse pleckstrin homology domain‐interacting protein (PHIP) is required for postnatal growth
Author(s) -
Li Shuai,
Francisco Adam B.,
Han Chunchun,
Pattabiraman Shrivatsav,
Foote Monica R.,
Giesy Sarah L.,
Wang Chong,
Schimenti John C.,
Boisclair Yves R.,
Long Qiaoming
Publication year - 2010
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2010.08.042
Subject(s) - pleckstrin homology domain , gene isoform , protein kinase b , irs1 , proto oncogene proteins c akt , mutant , biology , phosphorylation , microbiology and biotechnology , cell growth , medicine , endocrinology , receptor , insulin receptor , chemistry , biochemistry , insulin , gene , insulin resistance
PHIP was isolated as an insulin receptor substrate 1 (IRS‐1) interacting protein. To date, the physiological roles of PHIP remain unknown. Here we show that mice lacking PHIP1, the full‐length isoform of PHIP, are born at normal size but suffer a 40% growth deficit by weaning. PHIP1 mutant mice develop hypoglycemia and have an average lifespan of 4–5 weeks. PHIP1‐deficient mouse embryonic fibroblasts (MEFs) grow markedly slower than wild‐type MEFs, but exhibit normal AKT phosphorylation and an increased cell proliferation in response to IGF‐1 treatment. Together these results suggest that PHIP1 regulates postnatal growth in an IGF‐1/AKT pathway‐independent manner.