title: Regulation of IGF-1/PI3K/Akt signalling by the phosphoinositide phosphatase pharbin.
abstract: Pharbin, a 5-phosphatase that induces arborization, is one of the phosphoinositide 5-phosphatases that is highly mutated in patients with Joubert syndrome. Pharbin can hydrolyse PI(4,5)P(2) and PI(3,4,5)P(3) and has the same substrate specificity as SHIP2 and SKIP, which negatively regulate PI3K signalling. Here, we investigated the role of pharbin in IGF-1/PI3K signalling. Ectopic expression of pharbin markedly suppressed the IGF-1-induced activation of Akt without affecting p42/44 MAP kinase phosphorylation. In contrast, pharbin silencing by RNA interference increased the IGF-1-induced phosphorylation of Akt, suggesting that pharbin negatively regulates PI3K/Akt signalling. Pharbin expression also inhibited the phosphorylation of p70 S6 kinase and 4E-BP1 as well as the subsequent protein synthesis in response to IGF-1 treatment. Taken together, these results indicate that pharbin is an important negative regulator of IGF-1/PI3K/Akt signalling and protein synthesis.
authors: Department of Molecular Oncology, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University Tokyo, Japan.
authors: Feng
authors: F
authors: Wang
authors: Takeshi
authors: T
authors: Ijuin
authors: Toshiki
authors: T
authors: Itoh
authors: Tadaomi
authors: T
authors: Takenawa
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000256:Adenoviridae; D000818:Animals; D018797:Cell Cycle Proteins; D015870:Gene Expression; D020868:Gene Silencing; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010750:Phosphoproteins / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D051381:Rats; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013379:Substrate Specificity; D000099182:Phosphoinositide 5-Phosphatases
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D010716:Phosphatidylinositols; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010750:Phosphoproteins; D010744:Phosphoric Monoester Hydrolases; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D000099182:Phosphoinositide 5-Phosphatases; C087000:EIF4EBP1 protein, human; C118303:phosphoinositide-3,4,5-triphosphate; C089504:polyphosphoinositide phosphatase