%0 Journal Article %A Schwarzer, Dirk %A Zhang, Zhongsen %A Zheng, Weiping %A Cole, Philip A. %D 2006 %T Negative Regulation of a Protein Tyrosine Phosphatase by Tyrosine Phosphorylation %U https://acs.figshare.com/articles/journal_contribution/Negative_Regulation_of_a_Protein_Tyrosine_Phosphatase_by_Tyrosine_Phosphorylation/3229264 %R 10.1021/ja0585174.s001 %2 https://acs.figshare.com/ndownloader/files/5063332 %K growth factor stimulation %K dephosphorylating phosphotyrosine peptides %K Protein Tyrosine Phosphatase %K weight protein tyrosine phosphatase %K tyrosine phosphorylation modifications %K tyrosine phosphatase %K tyrosine phosphorylation %K LMW %K PDGF %X The low molecular weight protein tyrosine phosphatase (LMW−PTP) is a ubiquitously expressed enzyme with several proposed roles in cell signaling. Previously, two tyrosine phosphorylation modifications of LMW−PTP at sites Tyr-131 and Tyr-132 in response to growth factor stimulation have been mapped and suggested to stimulate LMW−PTP phosphatase activity. Biochemical analysis of tyrosine phosphorylation of a tyrosine phosphatase is challenging because of the intrinsic instability of these modifications. Here we used expressed protein ligation to site-specifically incorporate a phosphotyrosine mimic (phosphonomethylenephenylalanine, Pmp) at the Tyr-131 and Tyr-132 positions and measured the catalytic activity of these semisynthetic LMW−PTPs. The phosphonate-modified LMW−PTPs were 10- to 23-fold less active in dephosphorylating phosphotyrosine peptides derived from the PDGF receptor and p190RhoGap, two putative cellular substrates. These findings suggest the first example of a tyrosine phosphatase that is inhibited by tyrosine phosphorylation and provide a new model for the regulation of LMW−PTP and its role in cell adhesion. %I ACS Publications