Intramolecular interactions between the juxtamembrane domain and phosphatase domains of receptor protein-tyrosine phosphatase RPTPμ -: Regulation of catalytic activity

被引:26
作者
Feiken, E [1 ]
van Etten, I [1 ]
Gebbink, MFBG [1 ]
Moolenaar, WH [1 ]
Zondag, GCM [1 ]
机构
[1] Netherlands Canc Inst, Div Cellular Biochem, NL-1066 CX Amsterdam, Netherlands
关键词
D O I
10.1074/jbc.275.20.15350
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
RPTP mu is a receptor-like protein-tyrosine phosphatase (RPTP) whose ectodomain mediates homotypic cell-cell interactions. The intracellular part of RPTP mu contains a relatively long juxtamembrane domain (158 amino acids; aa) and two conserved phosphatase domains (C1 and C2), The membrane-proximal C1 domain is responsible for the catalytic activity of RPTP mu, whereas the membrane-distal C2 domain serves an unknown function. The regulation of RPTP activity remains poorly understood, although dimerization has been proposed as a general mechanism of inactivation. Using the yeast two-hybrid system, we find that the C1 domain binds to an N-terminal noncatalytic region in RPTP mu, termed JM (aa 803-955), consisting of a large part of the juxtamembrane domain (120 as) and a small part of the C1 domain (33 as). When co-expressed in COS cells, the JM polypeptide binds to both the C1 and the C2 domain. Strikingly, the isolated JM polypeptide fails to interact with either full-length RPTP mu or with truncated versions of RPTP mu that contain the JM region, consistent with the dM-C1 and JM-C2 interactions being intramolecular rather than intermolecular, Furthermore, we find that large part of the juxtamembrane domain (aa 814-922) is essential for C1 to be catalytically active. Our findings suggest a model in which RPTP mu activity is regulated by the juxtamembrane domain undergoing intramolecular interactions with both the C1 and C2 domain.
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页码:15350 / 15356
页数:7
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