Intra- and intermolecular interactions between intracellular domains of receptor protein-tyrosine phosphatases
Intra- and intermolecular interactions between intracellular domains of receptor protein-tyrosine phosphatases
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DOI：
10.1074/jbc.m205810200
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发表时间：
2002-12-06
影响因子：
4.8
通讯作者：
den Hertog, J
中科院分区：
文献类型：
--
作者：
Blanchetot, C;Tertoolen, LG;den Hertog, J
存在两个蛋白酪氨酸磷酸酶（PTP）结构域是大多数跨膜受体PTP（RPTP）的显著特征。通常无活性的膜远端PTP结构域（RPTP-D2）结合并被提议调节膜近端PTP结构域（RPTP-D1）。我们开始描述RPTP-D1和RPTP-D2之间的相互作用，在体内通过免疫共沉淀的血凝素标记的融合蛋白编码的跨膜结构域和RPTP-D1和myc标记的RPTP-D2。使用了来自四个不同亚家族的七种RPTP：RPTPalpha、RPTPeptide、LAR、RPTPsigma、RPTPdelta、CD 45和RPTPmu。我们发现RPTP-D2与RPTPs的结合亲和力不同。内在RPTP-D2的存在改变了对其他RPTP-D2的结合特异性，这取决于RPTPs的身份。此外，RPTP-D2的C末端和RPTP-D1的“楔形”在结合特异性中起着中心作用。最后，全长RPTPa和LAR异源二聚化的氧化应激依赖性的方式。与RPTPalpha-D2一样，LAR-D2构象也受到氧化应激的影响，这表明RPTP复合物形成的共同调控机制。总的来说，RPTP-D1和RPTP-D2之间的相互作用是一种常见但特异的机制，可能受到调控。RPTP-D2和楔形结构是结合特异性的关键决定因素，从而调节RPTP之间的串扰。
The presence of two protein-tyrosine phosphatase (PTP) domains is a striking feature in most transmembrane receptor PTPs (RPTPs). The generally inactive membrane-distal PTP domains (RPTP-D2s) bind and are proposed to regulate the membrane-proximal PTP domains (RPTP-D1s). We set out to characterize the interactions between RPTP-D1s and RPTP-D2s in vivo by co-immunoprecipitation of hemagglutinin-tagged fusion proteins encoding the transmembrane domain and RPTP-D1 and myc-tagged RPTP-D2. Seven RPTPs from four different subfamilies were used: RPTPalpha, RPTPepsilon, LAR, RPTPsigma, RPTPdelta, CD45, and RPTPmu. We found that RPTP-D2s bound to RPTPs with different affinities. The presence of intrinsic RPTP-D2 altered the binding specificity toward other RPTP-D2s positively or negatively, depending on the identity of the RPTPs. Furthermore, the C terminus of RPTP-D2s and the "wedge" in RPTP-D1s played a central role in binding specificity. Finally, full-length RPTPa and LAR heterodimerized in an oxidative stress-dependent manner. Like RPTPalpha-D2, the LAR-D2 conformation was affected by oxidative stress, suggesting a common regulatory mechanism for RPTP complex formation. Taken together, interactions between RPTP-D1s and RPTP-D2s are a common but specific mechanism that is likely to be regulated. The RPTP-D2s and the wedge structures are crucial determinants of binding specificity, thus regulating crosstalk between RPTPs.