Intra- and Intermolecular Interactions between Intracellular Domains of Receptor Protein-tyrosine Phosphatases

摘要: Abstract The presence of two protein-tyrosine phosphatase (PTP) domains is a striking feature in most transmembrane receptor PTPs (RPTPs). generally inactive membrane-distal PTP (RPTP-D2s) bind and are proposed to regulate the membrane-proximal (RPTP-D1s). We set out characterize interactions between RPTP-D1s RPTP-D2s vivo by co-immunoprecipitation hemagglutinin-tagged fusion proteins encoding domain RPTP-D1 myc-tagged RPTP-D2. Seven RPTPs from four different subfamilies were used: RPTPα, RPTPe, LAR, RPTPς, RPTPδ, CD45, RPTPμ. found that bound with affinities. intrinsic RPTP-D2 altered binding specificity toward other positively or negatively, depending on identity RPTPs. Furthermore, C terminus “wedge” played central role specificity. Finally, full-length RPTPα LAR heterodimerized an oxidative stress-dependent manner. Like RPTPα-D2, LAR-D2 conformation was affected stress, suggesting common regulatory mechanism for RPTP complex formation. Taken together, but specific likely be regulated. wedge structures crucial determinants specificity, thus regulating cross-talk