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PMID:16399794
| Citation |
Berger, P, Berger, I, Schaffitzel, C, Tersar, K, Volkmer, B and Suter, U (2006) Multi-level regulation of myotubularin-related protein-2 phosphatase activity by myotubularin-related protein-13/set-binding factor-2. Hum. Mol. Genet. 15:569-79 |
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| Abstract |
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. |
| Links |
PubMed Online version:10.1093/hmg/ddi473 |
| Keywords |
Animals; Binding Sites; COS Cells; Cercopithecus aethiops; Charcot-Marie-Tooth Disease/enzymology; Charcot-Marie-Tooth Disease/genetics; Enzyme Activation/genetics; Humans; Mice; Multiprotein Complexes/genetics; Multiprotein Complexes/metabolism; Protein Binding; Protein Structure, Quaternary; Protein Tyrosine Phosphatases/genetics; Protein Tyrosine Phosphatases/metabolism; Protein Tyrosine Phosphatases, Non-Receptor |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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