Berger P Berger I Schaffitzel C Tersar K Volkmer B Suter U 2006 Mutations in myotubularin-related protein-2 (MTMR2) or MTMR13/set-binding factor-2 (SBF2) genes are responsible for the severe autosomal recessive hereditary neuropathies, Charcot-Marie-Tooth disease (CMT) types 4B1 and 4B2, both characterized by reduced nerve conduction velocities, focally folded myelin sheaths and demyelination. MTMRs form a large family of conserved dual-specific phosphatases with enzymatically active and inactive members. We show that homodimeric active Mtmr2 interacts with homodimeric inactive Sbf2 in a tetrameric complex. This association dramatically increases the enzymatic activity of the complexed Mtmr2 towards phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate. Mtmr2 and Sbf2 are considerably, but not completely, co-localized in the cellular cytoplasm. On membranes of large vesicles formed under hypo-osmotic conditions, Sbf2 favorably competes with Mtmr2 for binding sites. Our data are consistent with a model suggesting that, at a given cellular location, Mtmr2 phosphatase activity is highly regulated, being high in the Mtmr2/Sbf2 complex, moderate if Mtmr2 is not associated with Sbf2 or functionally blocked by competition through Sbf2 for membrane-binding sites. application/pdf https://sonar.ch/global/documents/71635 eng info:eu-repo/semantics/altIdentifier/doi/10.1093/hmg/ddi473 info:eu-repo/semantics/altIdentifier/pmid/16399794 info:eu-repo/semantics/openAccess Human molecular genetics. - 2006 Animals Binding Sites COS Cells Charcot-Marie-Tooth Disease Chlorocebus aethiops Enzyme Activation Humans Mice Multiprotein Complexes Protein Binding Protein Structure, Quaternary Protein Tyrosine Phosphatases Protein Tyrosine Phosphatases, Non-Receptor Multi-level regulation of myotubularin-related protein-2 phosphatase activity by myotubularin-related protein-13/set-binding factor-2. http://purl.org/coar/resource_type/c_6501