The CMT4B disease-causing proteins MTMR2 and MTMR13/SBF2 regulate AKT signalling
Philipp Berger1, Kristian Tersar, Kurt Ballmer-Hofer
1Molecular Cell Biology, Paul Scherrer Institut, Villigen, Switzerland.
Journal of Cellular and Molecular Medicine
|November 17, 2009
Summary
Mutations in myotubularin-related protein-2 (MTMR2) and MTMR13/SBF2 genes disrupt cellular signaling. These proteins regulate epidermal growth factor receptor degradation and Akt activation, processes likely impaired in Charcot-Marie-Tooth disease type 4B.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Charcot-Marie-Tooth disease type 4B (CMT4B) is linked to mutations in MTMR2 and MTMR13/SBF2 genes.
- MTMR2 is a lipid phosphatase, while MTMR13/SBF2 is an inactive binding partner.
- Altered AKT signaling protein levels were observed in mouse mutants.
Purpose of the Study:
- To investigate the roles of MTMR2 and MTMR13/SBF2 in cellular signaling pathways.
- To understand how these proteins influence signaling processes relevant to CMT4B.
Main Methods:
- Analysis of signaling protein levels in mouse mutants.
- Overexpression studies of MTMR2 and MTMR13/SBF2.
- Assessment of epidermal growth factor receptor (EGFR) degradation and Akt/Erk activation.
Main Results:
- MTMR2 overexpression inhibits EGFR degradation, causing sustained Akt activation but not affecting Erk activation.
- MTMR13/SBF2 counteracts EGFR degradation blockage without impacting prolonged Akt activation.
- These findings highlight the involvement of MTMR2 and MTMR13/SBF2 in modulating cellular signaling.
Conclusions:
- MTMR2 and MTMR13/SBF2 are crucial for cellular signaling modulation and protein sorting.
- Dysregulation of these proteins likely contributes to the pathogenesis of CMT4B.
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