ArticleMolecular and cellular biology1998
The pleckstrin homology and phosphotyrosine binding domains of insulin receptor substrate 1 mediate inhibition of apoptosis by insulin.
Article in Molecular and cellular biology, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 80 citations in OpenAlex.
- Small Molecule Modulator of the mTORC2 Pathway Discovered from a DEL Library Designed to Bind to Pleckstrin Homology Domains.ACS chemical biology · 2024Article
- Disruption of insulin receptor substrate-2 impairs growth but not insulin function in rats.The Journal of biological chemistry · 2020Article
- A novel transcript is up-regulated by fasting in the hypothalamus and enhances insulin signalling.Journal of neuroendocrinology · 2013Article
- Ankyrin repeat and SOCS box containing protein 4 (Asb-4) colocalizes with insulin receptor substrate 4 (IRS4) in the hypothalamic neurons and mediates IRS4 degradation.BMC neuroscience · 2011Article
- Insulin signaling meets mitochondria in metabolism.Trends in endocrinology and metabolism: TEM · 2010Review
- Differential roles of CIDEA and CIDEC in insulin-induced anti-apoptosis and lipid droplet formation in human adipocytes.Journal of lipid research · 2010Article
- Insulin receptor substrate-2 mediated insulin-like growth factor-I receptor overexpression in pancreatic adenocarcinoma through protein kinase Cdelta.Cancer research · 2009Article
- Insulin receptor substrate (IRS)-1 regulates murine embryonic stem (mES) cells self-renewal.Journal of cellular physiology · 2007Article
- Role of the PI3-kinase/mTor pathway in the regulation of the stearoyl CoA desaturase (SCD1) gene expression by insulin in liver.Journal of cell communication and signaling · 2007Article
- Molecular mechanism of insulin resistance.Journal of biosciences · 2007Review
- Transformation by the simian virus 40 T antigen is regulated by IGF-I receptor and IRS-1 signaling.Oncogene · 2006Article
- Insulin reduces apoptosis and increases DNA synthesis and cell size via distinct signalling pathways in Drosophila Kc cells.Cell proliferation · 2004Article
- Article
- Placental overgrowth in mice lacking the imprinted gene Ipl.Proceedings of the National Academy of Sciences of the United States of America · 2002Article
- The role of the insulin receptor substrate-1 in the differentiation of rat hippocampal neuronal cells.Oncogene · 2001Article
- Regulation of Id gene expression by type I insulin-like growth factor: roles of Stat3 and the tyrosine 950 residue of the receptor.Molecular and cellular biology · 2001Article
- IGF-I receptor signalling in transformation and differentiation.Molecular pathology : MP · 2001Review
- Mechanisms of regulation of cell adhesion and motility by insulin receptor substrate-1 in prostate cancer cells.Oncogene · 2001Article
- Cellular compartmentalization in insulin action: altered signaling by a lipid-modified IRS-1.Molecular and cellular biology · 2000Article
- IRS-4 mediates protein kinase B signaling during insulin stimulation without promoting antiapoptosis.Molecular and cellular biology · 2000Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Insulin and insulin-like growth factor 1 (IGF-1) evoke diverse biological effects through receptor-mediated tyrosine phosphorylation of insulin receptor substrate (IRS) proteins. We investigated the elements of IRS-1 signaling that inhibit apoptosis of interleukin 3 (IL-3)-deprived 32D myeloid progenitor cells. 32D cells have few insulin receptors and no IRS proteins; therefore, insulin failed to inhibit apoptosis during IL-3 withdrawal. Insulin stimulated mitogen-activated protein kinase in 32D cells expressing insulin receptors (32DIR) but failed to activate the phosphatidylinositol 3 (PI 3)-kinase cascade or to inhibit apoptosis. By contrast, insulin stimulated the PI 3-kinase cascade, inhibited apoptosis, and promoted replication of 32DIR cells expressing IRS-1. As expected, insulin did not stimulate PI 3-kinase in 32DIR cells, which expressed a truncated IRS-1 protein lacking the tail of tyrosine phosphorylation sites. However, this truncated IRS-1 protein, which retained the NH2-terminal pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains, mediated phosphorylation of PKB/akt, inhibition of apoptosis, and replication of 32DIR cells during insulin stimulation. These results suggest that a phosphotyrosine-independent mechanism mediated by the PH and PTB domains promoted antiapoptotic and growth actions of insulin. Although PI 3-kinase was not activated, its phospholipid products were required, since LY294002 inhibited these responses. Without IRS-1, a chimeric insulin receptor containing a tail of tyrosine phosphorylation sites derived from IRS-1 activated the PI 3-kinase cascade but failed to inhibit apoptosis. Thus, phosphotyrosine-independent IRS-1-linked pathways may be critical for survival and growth of IL-3-deprived 32D cells during insulin stimulation.
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