Journal article
Overexpression of the Protein Phosphatase 2A Regulatory Subunit Bγ Promotes Neuronal Differentiation by Activating the MAP Kinase (MAPK) Cascade
The Journal of biological chemistry, Vol.277(44), pp.41525-41532
11/01/2002
DOI: 10.1074/jbc.M203767200
PMID: 12191994
Abstract
Protein serine/threonine phosphatase 2A (PP2A) is a multifunctional regulator of cellular signaling. Variable regulatory subunits associate with a core dimer of scaffolding and catalytic subunits and are postulated to dictate substrate specificity and subcellular location of the heterotrimeric PP2A holoenzyme. The role of brain-specific regulatory subunits in neuronal differentiation and signaling was investigated in the PC6-3 subline of PC12 cells. Endogenous Bbeta, Bgamma, and B'beta protein expression was induced during nerve growth factor (NGF)-mediated neuronal differentiation. Transient expression of Bgamma, but not other PP2A regulatory subunits, facilitated neurite outgrowth in the absence and presence of NGF. Tetracycline-inducible expression of Bgamma caused growth arrest and neurofilament expression, further evidence that PP2A/Bgamma can promote differentiation. In PC6-3 cells, but not non-neuronal cell lines, Bgamma specifically promoted long lasting activation of the mitogen-activated protein (MAP) kinase cascade, a key mediator of neuronal differentiation. Pharmacological and dominant-negative inhibition and kinase assays indicate that Bgamma promotes neuritogenesis by stimulating the MAP kinase cascade downstream of the TrkA NGF receptor but upstream or at the level of the B-Raf kinase. Mutational analyses demonstrate that the divergent N terminus is critical for Bgamma activity. These studies implicate PP2A/Bgamma as a positive regulator of MAP kinase signaling in neurons.
Details
- Title: Subtitle
- Overexpression of the Protein Phosphatase 2A Regulatory Subunit Bγ Promotes Neuronal Differentiation by Activating the MAP Kinase (MAPK) Cascade
- Creators
- Stefan Strack
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.277(44), pp.41525-41532
- DOI
- 10.1074/jbc.M203767200
- PMID
- 12191994
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Language
- English
- Date published
- 11/01/2002
- Academic Unit
- Pathology; Iowa Neuroscience Institute; Neuroscience and Pharmacology
- Record Identifier
- 9984040461202771
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