Insulin receptor substrate 1 and 2 (IRS1 and IRS2): What a tangled web we weave

Steven B. Watersand, Jeffrey E. Pessin

Research output: Contribution to journalComment/debatepeer-review

63 Scopus citations


The insulin receptor is a transmembrane tyrosine kinase that is essential for mediating multiple intracellular signalling cascades that lean ultimately to the biological actions of insulin. Tyrosine phosphorylation of the cytosolic proteins insulin receptor substrate 1 and 2 (IRS1 and IRS2) produces protein 'scaffolding' for the assembly of effector proteins containing Src homology 2 (SH2) domains, thereby generating multisubunit signalling complexes. Although IRS1 was originally isolated as a specific insulin receptor substrate, both IRS1 and IRS2 appear to play a broader role, functioning also as proximal substrates in growth hormone and cytokine receptor signalling. Current data establish IRS1 and IRS2 as critical effecters integrating various cell-type-specific signals into distinct, but overlapping, biological responses.

Original languageEnglish (US)
Pages (from-to)1-4
Number of pages4
JournalTrends in Cell Biology
Issue number1
StatePublished - Jan 1996
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology


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