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

Soo-A Kim; Panayiotis O Vacratsis; Ron Firestein; Michael L Cleary; Jack E Dixon

doi:10.1073/pnas.0431052100

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

Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4492-7. doi: 10.1073/pnas.0431052100. Epub 2003 Mar 31.

Authors

Soo-A Kim¹, Panayiotis O Vacratsis, Ron Firestein, Michael L Cleary, Jack E Dixon

Affiliation

¹ Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109-0606, USA.

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Amino Acid Sequence
Animals
Binding Sites
COS Cells
Carrier Proteins / chemistry
Carrier Proteins / genetics
Carrier Proteins / metabolism*
Cell Line
Dimerization
Humans
In Vitro Techniques
Intracellular Signaling Peptides and Proteins*
Molecular Sequence Data
Protein Structure, Tertiary
Protein Tyrosine Phosphatases / chemistry
Protein Tyrosine Phosphatases / genetics
Protein Tyrosine Phosphatases / metabolism*
Protein Tyrosine Phosphatases, Non-Receptor
Recombinant Fusion Proteins / chemistry
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / metabolism
Repetitive Sequences, Amino Acid
Sequence Homology, Amino Acid
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

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