Multiple interactions between receptor protein-tyrosine phosphatase (RPTP) α and membrane-distal protein-tyrosine phosphatase domains of various RPTPs

被引:52
作者
Blanchetot, C [1 ]
den Hertog, J [1 ]
机构
[1] Netherlands Inst Dev Biol, Hubrecht Lab, NL-3584 CT Utrecht, Netherlands
关键词
D O I
10.1074/jbc.275.17.12446
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
Receptor protein-tyrosine phosphatase (RPTP) alpha belongs to the large family of receptor protein-tyrosine phosphatases containing two tandem phosphatase domains. Most of the catalytic activity is retained in the first, membrane-proximal domain (RPTP alpha-D1), and little is known about the function of the second, membrane distal domain (RPTP alpha-D2). We investigated whether proteins bound to RPTP alpha using the two-hybrid system and found that the second domain of RPTP sigma interacted with the juxtamembrane domain of RPTP alpha, We confirmed this interaction by co-immunoprecipitation experiments. Furthermore, RPTP alpha not only interacted with RPTP sigma-D2 but also with RPTP alpha-D2, LAR-D2, RPTP delta-D2, and RPTP mu-D2, members of various RPTP subfamilies, although with different affinities. In the yeast two-hybrid system and in glutathione S-transferase pull-down assays, we show that the RPTP-D2s interacted directly with the wedge structure of RPTP alpha-D1 that has been demonstrated to be involved in inactivation of the RPTP alpha-D1/RPTP alpha-D1 homodimer, The interaction was specific because the equivalent wedge structure in LAR was unable to interact with RPTP alpha-D2 or LAR-D2. In vitro, we show that other interaction sites exist as well, including the C terminus of RPTP alpha-D2. The observation that RPTP alpha, but not LAR, bound to multiple RPTP-D2s with varying affinities suggests a specific mechanism of cross-talk between RPTPs that may regulate their biological function.
引用
收藏
页码:12446 / 12452
页数:7
相关论文
共 40 条
[1]   Structural basis for inhibition of receptor protein-tyrosine phosphatase-alpha by dimerization [J].
Bilwes, AM ;
denHertog, J ;
Hunter, T ;
Noel, JP .
NATURE, 1996, 382 (6591) :555-559
[2]   Restoration of potent protein-tyrosine phosphatase activity into the membrane-distal domain of receptor protein-tyrosine phosphataseα [J].
Buist, P ;
Zhang, YL ;
Keng, YF ;
Wu, L ;
Zhang, ZY ;
den Hertog, J .
BIOCHEMISTRY, 1999, 38 (03) :914-922
[3]   PTPμ regulates N-cadherin-dependent neurite outgrowth [J].
Burden-Gulley, SM ;
Brady-Kalnay, SM .
JOURNAL OF CELL BIOLOGY, 1999, 144 (06) :1323-1336
[4]   Protein-tyrosine phosphatases in development [J].
den Hertog, J .
MECHANISMS OF DEVELOPMENT, 1999, 85 (1-2) :3-14
[5]   PHOSPHORYLATION OF RECEPTOR PROTEIN-TYROSINE-PHOSPHATASE-ALPHA ON TYR789, A BINDING-SITE FOR THE SH3-SH2-SH3 ADAPTER PROTEIN GRB-2 IN-VIVO [J].
DENHERTOG, J ;
TRACY, S ;
HUNTER, T .
EMBO JOURNAL, 1994, 13 (13) :3020-3032
[6]   RECEPTOR PROTEIN-TYROSINE PHOSPHATASE-ALPHA ACTIVATES PP60(C-SRC) AND IS INVOLVED IN NEURONAL DIFFERENTIATION [J].
DENHERTOG, J ;
PALS, CEGM ;
PEPPELENBOSCH, MP ;
TERTOOLEN, LGJ ;
DELAAT, SW ;
KRUIJER, W .
EMBO JOURNAL, 1993, 12 (10) :3789-3798
[7]   Expression of receptor protein-tyrosine phosphatase alpha mRNA and protein during mouse embryogenesis [J].
denHertog, J ;
Overvoorde, J ;
deLaat, SW .
MECHANISMS OF DEVELOPMENT, 1996, 58 (1-2) :89-101
[8]  
DENHERTOG J, 1995, CELL GROWTH DIFFER, V6, P303
[9]   Tight association of GRB2 with receptor protein-tyrosine phosphatase alpha is mediated by the SH2 and c-terminal SH3 domains [J].
denHertog, J ;
Hunter, T .
EMBO JOURNAL, 1996, 15 (12) :3016-3027
[10]  
Desai CJ, 1997, DEVELOPMENT, V124, P1941