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PMID: 12668758 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Regulation of myotubularin-related (MTMR)2 phosphatidylinositol phosphatase by MTMR5, a catalytically inactive phosphatase.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 100 ·No. 8 ·2003-04-15 ·Pages 4492-7

Kim SA, Vacratsis PO, Firestein R, Cleary ML, Dixon JE

Abstract

The myotubularin (MTM) family constitutes one of the most highly conserved protein-tyrosine phosphatase subfamilies in eukaryotes. MTM1, the archetypal member of this family, is mutated in X-linked myotubular myopathy, whereas mutations in the MTM-related (MTMR)2 gene cause the type 4B1 Charcot-Marie-Tooth disease, a severe hereditary motor and sensory neuropathy. In this study, we identified a protein that specifically interacts with MTMR2 but not MTM1. The interacting protein was shown by mass spectrometry to be MTMR5, a catalytically inactive member of the MTM family. We also demonstrate that MTMR2 interacts with MTMR5 via its coiled-coil domain and that mutations in the coiled-coil domain of either MTMR2 or MTMR5 abrogate this interaction. Through this interaction, MTMR5 increases the enzymatic activity of MTMR2 and dictates its subcellular localization. This article demonstrates an active MTM member being regulated by an inactive family member.

MeSH Terms
Amino Acid Sequence Animals Binding Sites COS Cells Carrier Proteins/chemistry,genetics,metabolism Cell Line Dimerization Humans In Vitro Techniques Intracellular Signaling Peptides and Proteins Molecular Sequence Data Protein Structure, Tertiary Protein Tyrosine Phosphatases/chemistry,genetics,metabolism Protein Tyrosine Phosphatases, Non-Receptor Recombinant Fusion Proteins/chemistry,genetics,metabolism Repetitive Sequences, Amino Acid Sequence Homology, Amino Acid Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Chemicals
Carrier Proteins Intracellular Signaling Peptides and Proteins Recombinant Fusion Proteins SBF1 protein, human MTMR2 protein, human Protein Tyrosine Phosphatases Protein Tyrosine Phosphatases, Non-Receptor myotubularin
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Kim Soo-A
Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109-0606, USA.
Vacratsis Panayiotis O
Firestein Ron
Cleary Michael L
Dixon Jack E
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0431052100
Published
2003-04-15
Epub
2003-00-31
Pages
4492-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC153583
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.0431052100 PMC Full Text View journal details
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