Year: 2008
Type: article
Abstract: Protein tyrosine phosphatases (PTPs) are an important family of signal transduction proteins, together with protein tyrosine kinases, controlling tyrosine phosphorylation which plays a major role in many cellular functions including cell survival, proliferation, and differentiation.There are at least 107 genes coding for PTPs in the human genome.Recently, about half of all PTP genes have been implicated in human disease and recognized as potential drug targets.PTPs have a conserved catalytic domain and show some subtle structural differences in the active-site residues.The detailed structural information of PTPs will enable us to verify the interaction between substrates and the active-site residues and provide a solid foundation for rational PTP inhibitor design.To this end, the catalytic domains of 56 human PTPs (RPTPalpha, RPTPbeta, LAR, SAP1, DEP1, RPTPkappa, RPTPmu, IA-2, IA-2beta, PTP-U2, PCPTP, RPTPsigma, PTPRT, PTP1B, TCPTP, STEP, SHP1, HePTP, SHP2, PTP-BAS, PTP36, PTPD1, MKP-1, MKP-2, hVH3/B23, PYST1, PYST2, hVH5, MKP-4, MKP-5, MKP-7, VHR, PIR1, HYVH1, BEDP, TMDP, VHY, DUSP20, DUSP17, DUSP21, VHX, MOSP, MGC1136, VHZ, MCE, SSH1, SSH2, PRL1, PRL2, PRL3, CDC14B, LMPTP, CDC25A, CDC25B, CDC25C, Eya2) were well expressed in E. coli and subjected to the crystallization screening.Among them, more than 16 PTPs were successfully crystallized and some of their structural analyses have been reported.Especially with our recent structural report of SSH2, comparative analysis between seven sub-families (MKPs, atypical DSPs, SSHs, PRLs, CDC14s, PTENs, MTMs) of DSPs or VH1-like PTPs (61 genes) would be possible.With these results, our targeted proteomics research efforts involving mass spectrometric analysis will be also discussed.
Institutions: Scripps Research Institute, Joint Center for Structural Genomics, Korea Research Institute of Bioscience and Biotechnology, Stanford Synchrotron Radiation Lightsource, Jeju National University, Stanford University, Sanford Burnham Prebys Medical Discovery Institute, Sejong University, Genomics Institute of the Novartis Research Foundation, University of California San Diego
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W2318143376