ArticleMolecular and cellular biology1994
Microinjection of the SH2 domain of the 85-kilodalton subunit of phosphatidylinositol 3-kinase inhibits insulin-induced DNA synthesis and c-fos expression.
Article in Molecular and cellular biology, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 129 citations in OpenAlex.
- Oncogenic N-Ras Stimulates SRF-Mediated Transactivation via H3 Acetylation at Lysine 9.BioMed research international · 2018Article
- Carboxy-terminal domain of Cas differentially modulatesAnimal cells and systems · 2018Article
- PKC-beta1 mediates glucose-induced Akt activation and TGF-beta1 upregulation in mesangial cells.Journal of the American Society of Nephrology : JASN · 2009Article
- Collagen I induction by high glucose levels is mediated by epidermal growth factor receptor and phosphoinositide 3-kinase/Akt signalling in mesangial cells.Diabetologia · 2007Article
- Neuregulin 1-Beta cytoprotective role in AML 12 mouse hepatocytes exposed to pentachlorophenol.International journal of environmental research and public health · 2006Article
- Quantitative immunodetection of key elements of polyphosphoinositide signal transduction in osteoblasts from arthritic patients shows a direct correlation with cell proliferation.Histochemistry and cell biology · 2005Article
- Kinase activation through dimerization by human SH2-B.Molecular and cellular biology · 2005Article
- SKIP negatively regulates insulin-induced GLUT4 translocation and membrane ruffle formation.Molecular and cellular biology · 2003Article
- Multiple developmental defects derived from impaired recruitment of ASC-2 to nuclear receptors in mice: implication for posterior lenticonus with cataract.Molecular and cellular biology · 2002Article
- Vps34p differentially regulates endocytosis from the apical and basolateral domains in polarized hepatic cells.The Journal of cell biology · 2001Article
- SRF-dependent gene expression is required for PI3-kinase-regulated cell proliferation.The EMBO journal · 2000Article
- Protein kinase A-dependent and -independent signaling pathways contribute to cyclic AMP-stimulated proliferation.Molecular and cellular biology · 1999Article
- Activating signal cointegrator 1, a novel transcription coactivator of nuclear receptors, and its cytosolic localization under conditions of serum deprivation.Molecular and cellular biology · 1999Article
- Intracellular movement of green fluorescent protein-tagged phosphatidylinositol 3-kinase in response to growth factor receptor signaling.The Journal of cell biology · 1999Article
- Arrest of endosome acidification by bafilomycin A1 mimics insulin action on GLUT4 translocation in 3T3-L1 adipocytes.The Biochemical journal · 1999Article
- Cyclin D1 expression mediated by phosphatidylinositol 3-kinase through mTOR-p70(S6K)-independent signaling in growth factor-stimulated NIH 3T3 fibroblasts.Molecular and cellular biology · 1999Article
- An SH2 domain-containing 5' inositolphosphatase inhibits insulin-induced GLUT4 translocation and growth factor-induced actin filament rearrangement.Molecular and cellular biology · 1999Article
- Distinct roles for the p110alpha and hVPS34 phosphatidylinositol 3'-kinases in vesicular trafficking, regulation of the actin cytoskeleton, and mitogenesis.The Journal of cell biology · 1998Article
- A function for phosphatidylinositol 3-kinase beta (p85alpha-p110beta) in fibroblasts during mitogenesis: requirement for insulin- and lysophosphatidic acid-mediated signal transduction.Molecular and cellular biology · 1998Article
- Atypical protein kinase Clambda binds and regulates p70 S6 kinase.The Biochemical journal · 1998Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
We have investigated the functional role of the SH2 domain of the 85-kDa subunit (p85) of the phosphatidylinositol 3-kinase in the insulin signal transduction pathway. Microinjection of a bacterial fusion protein containing the N-terminal SH2 domain of p85 inhibited insulin- and other growth factor-induced DNA synthesis by 90% and c-fos protein expression by 80% in insulin-responsive rat fibroblasts. The specificity of the fusion protein was examined by in vitro precipitation experiments, which showed that the SH2 domain of p85 can independently associate with both insulin receptor substrate 1 and the insulin receptor itself in the absence of detectable binding to other phosphoproteins. The microinjection results were confirmed through the use of an affinity-purified antibody directed against p85, which gave the same phenotype. Additional studies were carried out in another cell line expressing mutant insulin receptors which lack the cytoplasmic tyrosine residues with which p85 interacts. Microinjection of the SH2 domain fusion protein also inhibited insulin signaling in these cells, suggesting that association of p85 with insulin receptor substrate 1 is a key element in insulin-mediated cell cycle progression. In addition, coinjection of purified p21ras protein with the p85 fusion protein or the antibody restored DNA synthesis, suggesting that ras function is either downstream or independent of p85 SH2 domain interaction.
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