Journal article
Myelin protein zero/P0 phosphorylation and function require an adaptor protein linking it to RACK1 and PKCα
The Journal of cell biology, Vol.177(4), pp.707-716
05/21/2007
DOI: 10.1083/jcb.200608060
PMCID: PMC2064215
PMID: 17502419
Abstract
Point mutations in the cytoplasmic domain of myelin protein zero (P0; the major myelin protein in the peripheral nervous system) that alter a protein kinase Cα (PKCα) substrate motif (198HRSTK201) or alter serines 199 and/or 204 eliminate P0-mediated adhesion. Mutation in the PKCα substrate motif (R198S) also causes a form of inherited peripheral neuropathy (Charcot Marie Tooth disease [CMT] 1B), indicating that PKCα-mediated phosphorylation of P0 is important for myelination. We have now identified a 65-kD adaptor protein that links P0 with the receptor for activated C kinase 1 (RACK1). The interaction of p65 with P0 maps to residues 179–197 within the cytoplasmic tail of P0. Mutations or deletions that abolish p65 binding reduce P0 phosphorylation and adhesion, which can be rescued by the substitution of serines 199 and 204 with glutamic acid. A mutation in the p65-binding sequence G184R occurs in two families with CMT, and mutation of this residue results in the loss of both p65 binding and adhesion function.
Details
- Title: Subtitle
- Myelin protein zero/P0 phosphorylation and function require an adaptor protein linking it to RACK1 and PKCα
- Creators
- Ana-Maria Gaboreanu - Department of Biological Sciences, The University of Iowa, Iowa City, IA 52242Ronald Hrstka - Department of Biological Sciences, The University of Iowa, Iowa City, IA 52242Wenbo Xu - Department of Neurology, Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48202Michael Shy - Department of Neurology, Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48202John Kamholz - Department of Neurology, Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48202Jack Lilien - Department of Biological Sciences, The University of Iowa, Iowa City, IA 52242Janne Balsamo - Department of Biological Sciences, The University of Iowa, Iowa City, IA 52242
- Resource Type
- Journal article
- Publication Details
- The Journal of cell biology, Vol.177(4), pp.707-716
- DOI
- 10.1083/jcb.200608060
- PMID
- 17502419
- PMCID
- PMC2064215
- ISSN
- 0021-9525
- eISSN
- 1540-8140
- Language
- English
- Date published
- 05/21/2007
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Biology
- Record Identifier
- 9984014020902771
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