Linked Life Data

9305869

Source:http://linkedlifedata.com/resource/pubmed/id/9305869

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
39
pubmed:dateCreated
1997-10-23
pubmed:abstractText
In addition to a role in response to insulin and insulin-like growth factors, insulin receptor substrate 1 (IRS-1) is phosphorylated in response to IL-4, the interferons (IFNs) and oncostatin M (OSM). Here mutant cell lines lacking JAK1, JAK2, or Tyk2 were used to determine the role(s) of the Janus kinase (JAK) family of protein-tyrosine kinases in IRS-1 phophorylation. 32D cells, which do not express IRS proteins, were analyzed for any requirement for these proteins in response to the IFNs. For the mutant human fibrosarcoma cell lines, phosphorylation of IRS-1 through the insulin-like growth factor receptor is independent of JAK1, JAK2, or Tyk2. In contrast, phosphorylation of IRS-1 mediated by the Type I IFNs, IL-4, and OSM is JAK-dependent. For the alphabeta-IFNs, activation of IRS-1 is dependent on JAK1 and Tyk2, consistent with the interdependence of these kinases in the IFN-alphabeta response. Neither IRS-1 nor IRS-2 was detectably activated by IFN-gamma. Consistent with this, activation of neither IRS proteins appears to be an absolute requirement for an antiproliferative or an antiviral response to the IFNs. For IL-4 and OSM phosphorylation of IRS-1 in the human fibrosarcoma cells is largely dependent on JAK1 but can also be mediated through Tyk2 or JAK2. Activation of phosphatidylinositol 3'-kinase in response to IL-4 and OSM, at least, was also JAK-dependent. The JAKs are, therefore, required not only for STAT activation but also for the activation, through a variety of different types of cytokine receptor, of an additional signaling pathway(s) through IRS-1 and phosphatidylinositol 3'-kinase.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/IRS1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Insulin Receptor Substrate Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Interferons, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-4, http://linkedlifedata.com/resource/pubmed/chemical/JAK1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Janus Kinase 1, http://linkedlifedata.com/resource/pubmed/chemical/OSM protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Oncostatin M, http://linkedlifedata.com/resource/pubmed/chemical/Peptides, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Phosphotransferases (Alcohol Group..., http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Receptor, IGF Type 1
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
26
pubmed:volume
272
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
24183-90
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Janus kinase-dependent activation of insulin receptor substrate 1 in response to interleukin-4, oncostatin M, and the interferons.
pubmed:affiliation
Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't