Protein Phosphorylation in Astrocytes Mediated by Protein Kinase C: Comparison with Phosphorylation by Cyclic AMP‐Dependent Protein Kinase

Harrison, Beth C.; Mobley, Philip L.

doi:10.1111/j.1471-4159.1989.tb07421.x

Cited by 28 publications

(21 citation statements)

References 29 publications

(20 reference statements)

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“…Furthermore, most, and perhaps all, of the astrocytes in the optic nerve were immunostained. These results are in agreement with the previous localization of PKC type I11 ( a ) isozyme in cultured astroglial (Pollenz and McCarthy, 1985;Mobley et al, 1986;Neary et al, 1986Neary et al, , 1988Harrison and Mobley, 1989;Bhat, 1989).…”

Section: Discussionsupporting

confidence: 94%

Distribution of protein kinase C isozymes in rat optic nerves

Komoly

Liu

Webster

et al. 1991

J of Neuroscience Research

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Light (LM) and electron (EM) microscopic immunocytochemical methods were used to study the distribution of protein kinase C (PKC) isozymes in adult rat optic nerves. In cryostat and vibratome sections examined by LM, type II (beta) isozyme was localized almost exclusively in the axons. In the EM, immunoreaction products were found to associate with microtubules and neurofilaments. The inner surface of axonal membranes were occasionally stained. Analysis of PKC isozyme composition of the optic nerves by using immunoblot techniques revealed that type II (beta) isozyme accounted for approximately 80% of the total immunoreactivity. By contrast, type III (alpha) isozyme, which accounted for the remaining 20% of PKC, was found mainly in the astrocytes. Astrocytic processes next to blood vessels and between myelinated axons were stained. In the EM, immunoreaction products were found in the cytoplasm and along astroglial filaments. Segments of plasma membranes also were stained; but nuclei were unstained. Adult glial cells were not stained by an antibody to type II (beta) isozyme except for the occurrence of a few punctate cytoplasmic densities in occasional astrocytes. Very faint or no immunostaining was observed in sections treated with a monoclonal antibody to type I (gamma) isozyme. Immunoblot analyses also did not reveal this subspecies. The absence of type I (gamma) isozyme in optic nerves is not due to a down-regulation of the enzyme during development. In developing (5 and 11 day) rats, immunoreactivity of protein kinase C was very faint or absent. After 15 days, reaction products of both type III (alpha) and type II (beta) isozymes were found throughout the nerve. These findings suggest that type II (beta) isozyme may be involved in axonal transport whereas type III (alpha) isozyme may play a role in some astrocyte functions in mature optic nerves.

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Section: Discussionsupporting

confidence: 94%

Distribution of protein kinase C isozymes in rat optic nerves

Komoly

Liu

Webster

et al. 1991

J of Neuroscience Research

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“…4; Table I) d e nonstrate that protein kinase C and a cyclic AMP-dependent kinase are both prcscnt in astrocytes and may be capable of phosphorylating GFAP. Similar findings have been rcported with cultured cells (Browing and Ruina, 1984;Pollenz and McCarthy, 1986;Harrison and Mobley? 1989).…”

Section: Discussionsupporting

confidence: 76%

Phosphorylation of the glial fibrillary acidic protein

Noetzel¹

1990

J of Neuroscience Research

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The glial fibrillary acidic protein (GFAP) was found to be phosphorylated in vivo after intracerebral injection of [32P]-orthophosphate, in brain slices, and in a cell free system. The phosphorylated proteins were separated by two-dimensional gel electrophoresis and then transferred to nitrocellulose sheets. Two isoelectric variants of GFAP were immunochemically identified by monoclonal antibodies. Autoradiography demonstrated that only the more acidic isoelectric variant of GFAP was phosphorylated. Phosphoamino acid analysis revealed that under all conditions GFAP was phosphorylated at serine and threonine residues. Incubation of brain slices with [32P]-orthophosphate and the protein kinase C activator phorbol 12-myristate 13-acetate or forskolin, an activator of cyclic AMP-dependent protein kinase, stimulated phosphorylation of GFAP. Likewise phosphorylation of GFAP was also accentuated by calcium/phosphatidylserine/diolein and by exogenous cyclic AMP-dependent kinase in a cell free system. These findings announce that protein kinase C and cyclic-AMP dependent kinase may play physiologic roles in the in situ phosphorylation of GFAP. When isolated cytoskeletal preparations were incubated with [gamma-32P] ATP, GFAP was phosphorylated in vitro by two additional protein kinases, a Ca2++/calmodulin-dependent kinase and an effector-independent kinase. The results of these investigations strongly suggest that phosphorylation of GFAP appears to be regulated by multiple second messenger pathways.

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“…It has been known for some years that IF proteins, including GFAP, undergo cyclic phosphorylation and dephosphorylation in intact cell preparations (52,53), but until recently information on the sites phosphorylated was lacking. These sites have now been described for porcine GFAP phosphorylated in vitro where six sites were identified by Japanese workers (47,54).…”

Section: General and Functional Aspects Of Gfap Phosphorylationmentioning

confidence: 99%

Control of the phosphorylation of the astrocyte marker glial fibrillary acidic protein (GFAP) in the immature rat hippocampus by glutamate and calcium ions: possible key factor in astrocytic plasticity

Rodnight¹,

Gonçalves²,

Wofchuk³

et al. 1997

Braz J Med Biol Res

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The present review describes recent research on the regulation by glutamate and Ca 2+ of the phosphorylation state of the intermediate filament protein of the astrocytic cytoskeleton, glial fibrillary acidic protein (GFAP), in immature hippocampal slices. The results of this research are discussed against a background of modern knowledge of the functional importance of astrocytes in the brain and of the structure and dynamic properties of intermediate filament proteins. Astrocytes are now recognized as partners with neurons in many aspects of brain function with important roles in neural plasticity. Site-specific phosphorylation of intermediate filament proteins, including GFAP, has been shown to regulate the dynamic equilibrium between the polymerized and depolymerized state of the filaments and to play a fundamental role in mitosis. Glutamate was found to increase the phosphorylation state of GFAP in hippocampal slices from rats in the post-natal age range of 12-16 days in a reaction that was dependent on external Ca 2+ . The lack of external Ca 2+ in the absence of glutamate also increased GFAP phosphorylation to the same extent. These effects of glutamate and Ca 2+ were absent in adult hippocampal slices, where the phosphorylation of GFAP was completely Ca 2+ -dependent. Studies using specific agonists of glutamate receptors showed that the glutamate response was mediated by a G protein-linked group II metabotropic glutamate receptor (mGluR). Since group II mGluRs do not act by liberating Ca 2+ from internal stores, it is proposed that activation of the receptor by glutamate inhibits Ca 2+ entry into the astrocytes and consequently down-regulates a Ca 2+ -dependent dephosphorylation cascade regulating the phosphorylation state of GFAP. The functional significance of these results may be related to the narrow developmental window when the glutamate response is present. In the rat brain this window corresponds to the period of massive synaptogenesis during which astrocytes are known to proliferate. Possibly, glutamate liberated from developing synapses during this period may signal an increase in the phosphorylation state of GFAP and a consequent increase in the number of mitotic astrocytes.

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Protein Phosphorylation in Astrocytes Mediated by Protein Kinase C: Comparison with Phosphorylation by Cyclic AMP‐Dependent Protein Kinase

Cited by 28 publications

References 29 publications

Distribution of protein kinase C isozymes in rat optic nerves

Distribution of protein kinase C isozymes in rat optic nerves

Phosphorylation of the glial fibrillary acidic protein

Control of the phosphorylation of the astrocyte marker glial fibrillary acidic protein (GFAP) in the immature rat hippocampus by glutamate and calcium ions: possible key factor in astrocytic plasticity

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