The CMT4B disease-causing proteins MTMR2 and MTMR13/SBF2 regulate AKT signaling

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J Cell Mol Med. 2009 Nov 13. [Epub ahead of print]

The CMT4B disease-causing proteins MTMR2 and MTMR13/SBF2 regulate AKT signaling.

Berger P, Tersar K, Ballmer-Hofer K, Suter U.

Molecular Cell Biology, Scherrer Institut, CH-5232 Villigen, Switzerland.

Abstract

Charcot-Marie-Tooth disease type 4B is caused by mutations in the genes encoding

either the lipid phosphatase Myotubularin-Related-Protein-2 (MTMR2) or its

regulatory binding partner MTMR13/SBF2. Mtmr2 dephosphorylates PI-3-P and

PI-3,5-P2 to form phosphatidylinositol and PI-5-P, respectively, while

Mtmr13/Sbf2 is an enzymatically inactive member of the myotubularin protein

family.

We have found altered levels of the critical signaling protein AKT in mouse

mutants for Mtmr2 and Mtmr13/Sbf2. Thus, we analyzed the influence of Mtmr2 and

Mtmr13/Sbf2 on signaling processes.

We found that overexpression of Mtmr2 prevents the degradation of the epidermal

growth factor receptor (EGFR) and leads to sustained Akt activation whereas Erk

activation is not affected. Mtmr13/Sbf2 counteracts the blockage of EGFR

degradation without affecting prolonged Akt activation.

Our data indicate that Mtmr2 and Mtmr13/Sbf2 play critical roles in the sorting

and modulation of cellular signaling which are likely to be disturbed in CMT4B.