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The full-length isoform of the mouse pleckstrin homology domain-interacting protein (PHIP) is required for postnatal growth.

ABSTRACT: 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.

SUBMITTER: Li S

PROVIDER: S-EPMC2965186 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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The full-length isoform of the mouse pleckstrin homology domain-interacting protein (PHIP) is required for postnatal growth.

Li Shuai S Francisco Adam B AB Han Chunchun C Pattabiraman Shrivatsav S Foote Monica R MR Giesy Sarah L SL Wang Chong C Schimenti John C JC Boisclair Yves R YR Long Qiaoming Q

FEBS letters 20100904 18

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 i ...[more]

PMID: 20816727

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