The full-length isoform of the mouse pleckstrin homology domain-interacting protein (PHIP) is required for postnatal growth.
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.
Li
Shuai
S
Department of Animal Science, College of Agricultural and Life Sciences, Cornell University, Ithaca, NY 14850, USA.
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
D000818:Animals; D049109:Cell Proliferation; D005183:Failure to Thrive / Q000235:genetics*; D005260:Female; D007003:Hypoglycemia / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C420744:Phip protein, mouse; D020033:Protein Isoforms; D007334:Insulin-Like Growth Factor I; D051057:Proto-Oncogene Proteins c-akt
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