Tyrosine phosphorylation of IRS-1/2 (insulin receptor substrate 1 or 2) is an activation signal in the signal transduction pathway of insulin receptor. The phosphorylation is catalyzed by the beta-subunits of insulin receptor that is formed by two alpha and two beta subunits. The beta subunits are auto-phosphorylated on tyrosine residues and thus become activated upon insulin engagement with the alpha subunit. Tyrosine phopshorylation of IRS-1/2 leads to activation of down-stream signaling molecule PI3K by recruiting the regulatory subunit p85. Tyrosine phosphorylation in IRS and IR is require for insulin action and subject to regulation by tyrosine de-phosphorylation. Several tyrosine phosphatases have been identified for inhibition of these tyrosine phosphorylation-mediated events, such as PTP-1B whose activity contributes to insulin resistance. In Nature and Cell Metabolism, two more protein tyrosine phosphatases were reported to regulate insulin action especially in the liver: one is SHP-1 and the other is PTP-MEG2. See attached PDF files.

HP-1 and insulin signaling by Dubois 2006.pdf (417541 bytes)
PTP-MEG2 and insulin signaling by Cho 2006.pdf (570369 bytes)

By Jianping at PBRC
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Jianping Ye, MD
Associate Professor
Pennington Biomedical Research Center
Louisiana State University System
6400 Perkins Road
Baton Rouge, LA 70808
Phone: (225) 763-3163
Fax: (225) 763-2525
E-mail: yej@pbrc.edu