Multimerization of the protein-tyrosine phosphatase (PTP)-like insulin-dependent diabetes mellitus autoantigens IA-2 and IA-2beta with receptor PTPs (RPTPs). Inhibition of RPTPalpha enzymatic activity
| Autor: | Gross, S., Blanchetot, C., Schepens, J.T.G., Albet, S., Lammers, J.M., Hertog, J.F. den, Hendriks, W.J.A.J. |
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| Rok vydání: | 2002 |
| Předmět: | |
| Zdroj: | Journal of Biological Chemistry, 277, 50, pp. 48139-45 Journal of Biological Chemistry, 277, 48139-45 |
| ISSN: | 1083-351X |
| Popis: | Contains fulltext : 185410.pdf (Publisher’s version ) (Open Access) Most receptor-type protein-tyrosine phosphatases (RPTPs) contain two tandem PTP domains. For some RPTPs the enzymatically inactive membrane-distal phosphatase domains (D2) were found to bind enzymatically active membrane proximal PTP (D1) domains, and oligomerization has been proposed as a general regulatory mechanism. The RPTP-like proteins IA-2 and IA-2beta, major autoantigens in insulin-dependent diabetes mellitus, contain just a single enzymatically inactive PTP-like domain. Their physiological role is as yet enigmatic. To investigate whether the catalytically inactive cytoplasmic domains of IA-2 and IA-2beta are involved in oligomerization, we exploited interaction trap assay in yeast and glutathione S-transferase pull-down and co-immunoprecipitation strategies on lysates of transfected COS-1 cells. The results show that IA-2 and IA-2beta are capable of homo- and heterodimerization to which both the juxtamembrane region and the phosphatase-like segment can contribute. Furthermore, they can form heterodimers with some other RPTP members, most notably RPTPalpha and RPTPepsilon, and down-regulate RPTPalpha enzymatic activity. Thus, in addition to homo-dimerization, the enzymatic activity of receptor-type PTPs can be regulated through heterodimerization with other RPTPs, including the catalytically inactive IA-2 and IA-2beta. |
| Databáze: | OpenAIRE |
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