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PTP catalytic mechanism. the general acid. the general base. WPD loop. D to A mutant. DA (trapping) PTPs. WT (active) PTPs. PTP1B +/+. PTP1B -/-. Background PTP1B Knock Out Mice. PTP1B -/- mice display enhanced sensitivity to insulin
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PTP catalytic mechanism the general acid the general base
WPD loop D to A mutant
DA (trapping) PTPs WT (active) PTPs
PTP1B +/+ PTP1B -/- Background PTP1B Knock Out Mice PTP1B -/- mice display enhanced sensitivity to insulin PTP1B -/- mice are resistant to development of obesity and Type 2 diabetes (Elchebly et al. Science (1999) 83, 1544-1548)(Klaman et al. Mol Cell Biol (2000) 20, 5479-89)
PTP Inhibition of the Insulin Receptor PTP may Enhance Insulin Signaling Prolonged or Enhanced Signal Transient Signal
Structure of the PTP1B-IR peptide complex G1166 R1164 Phe182 Arg24 Arg254 pY1163 pY1162 Asp48 D1161 Tyr46 Arg47
IRTK Activation segment: DIpY1158ETDpY1162pY1163RKGG S.R. Hubbard, (1997) EMBO J., 16, 5573-5581
Kinetic Constants for Dephosphorylation of IR Activation Loop Peptide by PTP1B RDIpY1158ETDpY1162pY1163RKGGKGLL
Insulin Insulin Receptor PTK PTP1B Signaling Response PTP1B and insulin signaling
PTP Suppression of PTP1B expression by RNAi may enhance tyrosine phosphorylation of IR 972 1158 1162 1163 Prolonged or Enhanced Signal Transient Signal