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J. Biol. Chem., Vol. 277, Issue 50, 48139-48145, December 13, 2002
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From the 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-2
Multimerization of the Protein-tyrosine Phosphatase (PTP)-like
Insulin-dependent Diabetes Mellitus Autoantigens IA-2 and
IA-2
with Receptor PTPs (RPTPs)
INHIBITION OF RPTP
ENZYMATIC ACTIVITY*
§,,
,,**
Department of Cell Biology, Nijmegen Center
for Molecular Life Sciences, University of Nijmegen, Nijmegen 6525 GA
and the ¶ Hubrecht Laboratory, Utrecht 3584 CT, The Netherlands
and the Department of Internal Medicine IV, Tübingen
72076, Germany
, 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-2 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-2 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 RPTP and
RPTP
, and down-regulate RPTP 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-2.
*
This work was supported by the European Community Research
Fund.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
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