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01-11-2007 | Original Article

CCM3 interacts with CCM2 indicating common pathogenesis for cerebral cavernous malformations

Authors: Katrin Voss, Sonja Stahl, Elisa Schleider, Sybille Ullrich, Joachim Nickel, Thomas D. Mueller, Ute Felbor

Published in: Neurogenetics | Issue 4/2007

Abstract

Individuals carrying a mutation in one of the three cerebral cavernous malformation genes (CCM1/KRIT1, CCM2, CCM3) cannot be clinically distinguished, raising the possibility that they act within common molecular pathways. In this study, we demonstrate that CCM3 (PDCD10) coprecipitates and colocalizes with CCM2. We also show that CCM3 directly binds to serine/threonine kinase 25 (STK25, YSK1, SOK1) and the phosphatase domain of Fas-associated phosphatase-1 (FAP-1, PTPN13, PTP-Bas, PTP-BL). CCM3 is phosphorylated by STK25 but not by its other Yeast-Two hybrid interactor STK24, whereas the C-terminal catalytic domain of FAP-1 dephosphorylates CCM3. Finally, our experiments reveal that STK25 forms a protein complex with CCM2. Thus, our data link two proteins of unknown function, CCM3 and STK25, with CCM2, which is part of signaling pathways essential for vascular development and CCM pathogenesis.

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Title: CCM3 interacts with CCM2 indicating common pathogenesis for cerebral cavernous malformations
Authors: Katrin Voss
Sonja Stahl
Elisa Schleider
Sybille Ullrich
Joachim Nickel
Thomas D. Mueller
Ute Felbor
Publication date: 01-11-2007
Publisher: Springer-Verlag
Published in: Neurogenetics / Issue 4/2007
Print ISSN: 1364-6745
Electronic ISSN: 1364-6753
DOI: https://doi.org/10.1007/s10048-007-0098-9

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CCM3 interacts with CCM2 indicating common pathogenesis for cerebral cavernous malformations

Abstract

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Abstract

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