Sheu, F. S., Azmitia, E. C., Marshak, D. R., Parker, P. J., Routtenberg, A. (January 1994) Glial-Derived S100b Protein Selectively Inhibits Recombinant Beta-Protein Kinase-C (Pkc) Phosphorylation of Neuron-Specific Protein F1/Gap43. Molecular Brain Research, 21 (1-2). pp. 62-66. ISSN 0169-328X
Abstract
Protein F1/GAP43 is neuron-specific, associated with neurite outgrowth during development and a substrate for PKC. This protein is present in high levels in serotonergic neurons which in culture sprout in response to the glial-derived Sl00b, the beta-beta homodimer. As an initial step in determining whether S100b acts on F1/GAP43 we studied the regulation by Sl00b of PKC phosphorylation of F1/GAP43. Either the S100b or a mixture of S100a and S100b, both from a brain glial cell source, inhibited in vitro phosphorylation of purified F1/GAP43 by purified PKC in a dose-dependent manner. Using recombinant PKC subtypes, purified S100b preferentially inhibited the F1/GAP43 phosphorylation by the beta subtype. The IC50 of S100b for beta I and beta II PKC was 8 mu M while for alpha and gamma PKC it was 64 mu M. S100b inhibition was thus subtype-selective. Histone III-S phosphorylation by the four PKC subtypes was not inhibited by S100b. S100b inhibition was thus substrate-selective. Moreover, the effect of S100b on phosphorylation could not be explained by a direct inhibition of kinase activity. Together with earlier studies implicating a role for S100 in synaptic plasticity and neurite outgrowth, the present results suggest that S100b may regulate such functions through its inhibition of neuron-specific PKC substrate (F1/GAP43) phosphorylation. The regulation of this neuron-specific substrate phosphorylation by glial S100 suggests the potential for a novel neuro-glial interaction. Finally, the location ofS100 gene on chromosome 21, trisomic in Down's syndrome, and over-expressed in this disorder, as well as in Alzheimer's disease, suggests a link to cognitive impairments in human.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | GLIAL S100B PROTEIN F1/GAP43 PROTEIN KINASE C SYNAPTIC PLASTICITY ALZHEIMERS DISEASE DOWNS SYNDROME CALMODULIN-BINDING-PROTEIN SEROTONERGIC GROWTH-FACTOR GAP-43 MESSENGER-RNA SYNAPTIC PLASTICITY BRAIN PROTEIN BOVINE BRAIN SUBSTRATE PURIFICATION S-100 RAT |
| Subjects: | organs, tissues, organelles, cell types and functions > cell types and functions > cell types > glia cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > glia cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > glia cells bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase > Protein kinase C |
| CSHL Authors: | |
| Communities: | CSHL labs |
| Depositing User: | Matt Covey |
| Date: | January 1994 |
| Date Deposited: | 24 Jun 2015 19:28 |
| Last Modified: | 24 Jun 2015 19:28 |
| URI: | https://repository.cshl.edu/id/eprint/31464 |
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