Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The P0 protein in mammalian PNS myelin is known to undergo several posttranslational modifications, such as glycosylation, acylation, sulfation, and phosphorylation. Phosphorylation of purified P0 protein in vitro was studied comparatively using three enzymes, i.e., calcium/phospholipid-dependent protein kinase (protein kinase C), calcium/calmodulin-dependent protein kinase II (CaM kinase II), and the catalytic subunit of cyclic AMP-dependent protein kinase (A kinase). The phosphorylation of P0 protein by CaM kinase II was the greatest, followed by that by protein kinase C; phosphorylation by A kinase, however, was much lower. In order to identify phosphorylation sites, P0 protein was phosphorylated with [32P]ATP and each kinase and then digested with lysylendopeptidase. The resulting phosphopeptides were isolated by HPLC. Subsequent amino acid sequence analysis and comparison with the known sequence of P0 protein revealed that Ser181 and Ser204 were strongly phosphorylated by both protein kinase C and CaM kinase II. In addition, Ser214 was also phosphorylated by protein kinase C, but not by CaM kinase II. Because all of these sites are located in the cytoplasmic domain of P0 protein, phosphorylation may be important for maintenance of the major dense line of PNS myelin.
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PMID:Phosphorylation of P0 glycoprotein in peripheral nerve myelin. 170 69

2',3' cyclic nucleotide-3'-phosphodiesterase (CNP) is phosphorylated in the peripheral nervous system after immunoprecipitation of myelin proteins radiolabeled in vivo, in nerve slices and in a cell-free system. Only radiolabeled phosphoserine was detected after partial acid hydrolysis of immunoprecipitated CNP. Two major phosphopeptides were resolved by two dimensional electrophoresis-chromatography after digestion with trypsin of CNP phosphorylated in the nerve slices. Phosphorylation of CNP was not stimulated a) by forskolin in the nerve slices and b) after incubation of purified nerve myelin with cAMP. However, CNP phosphorylation was increased after incubation of PNS myelin with catalytic unit of protein kinase A. Phosphorylation of the central nervous system myelin CNP was dramatically stimulated by cAMP. These results suggest that PKA may be absent from peripheral nerve myelin or CNP may not be accessible to this enzyme in the PNS. Incubation of nerve slices with phorbol 12 myristate-13-acetate caused a marked increase in the phosphorylation of CNP. These results provide strong evidence that CNP is phosphorylated in the PNS and its phosphorylation in vivo is in all probability regulated by protein kinase C.
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PMID:2',3'cyclic nucleotide-3'-phosphodiesterase in peripheral nerve myelin is phosphorylated by a phorbol ester-sensitive protein kinase. 216 8

The effects of the naturally occurring polyamines spermine and spermidine on phosphorylation promoted by cyclic AMP (cAMP)-dependent protein kinase (PK) (cAMP-PK; EC 2.7.1.37) were studied using the brain of the tobacco hornworm, Manduca sexta. Four particulate-associated peptides (280, 34, 21, and 19 kilodaltons) in day 1 pupal brains are endogenous substrates for a particulate type II cAMP-PK. These phosphoproteins are present in brain synaptosomal, as well as microsomal, particulate fractions but are not present in the cytosol. They are distributed throughout the CNS and PNS and are present in several nonneuronal tissues as well. Phosphorylation of these proteins via cAMP-PK was inhibited markedly by micromolar concentrations of spermine and spermidine. Other particulate-associated peptides phosphorylated via a Ca2+/calmodulin-PK or Ca2+ and cAMP-independent PKs were unaffected by polyamines, whereas the phosphorylation of a 260-kilodalton peptide was markedly enhanced. Spermine did not exert its inhibitory effect indirectly by enhancement of cAMP or ATP hydrolysis or via proteolysis, but its action appears to involve a substrate-directed inhibition of cAMP-PK-promoted phosphorylation as well as enhanced dephosphorylation. Although addition of spermine resulted in marked ribosome aggregation in synaptosomal and microsomal particulate fractions, this phenomenon was not involved in the inhibition of cAMP-PK-promoted phosphorylation.
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PMID:Polyamines differentially inhibit cyclic AMP-dependent protein kinase-mediated phosphorylation in the brain of the tobacco hornworm, Manduca sexta. 284 97

Myelin isolated from the peripheral (PNS) and central nervous system (CNS) of mouse contained a protein kinase which catalyzed phosphorylation of myelin proteins. In the case of CNS myelin, small and large basic proteins were phosphorylated whereas in the case of PNS myelin, a glycoprotein (Po) as well as other basic proteins (P1 and P2) were phosphorylated. Ca2+, but not adenosine 3',5'-monophosphate (cyclic AMP), markedly (5- to 10-fold) stimulated phosphorylation of PNS and CNS myelin proteins. There was no difference between the normal and dystrophic mouse CNS myelin phosphorylation. However, a marked decrease in the cauda equina PNS myelin phosphorylation ofthe dystrophic mouse was observed. Interestingly, the dystrophic sciatic nerve myelin phosphorylation, compared to normal, was higher.
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PMID:Calcium ion stimulated endogenous protein kinase catalyzed phosphorylation of peripheral and central nerve myelin proteins: comparison between normal and genetically dystrophic mouse. 615 63

Cyclic AMP-sensitive protein kinase activity has been found in suspensions of purified rabbit peripheral myelin. The enzyme phosphorylated the P0, "Y", X, P1, and P2 myelin proteins. Kinase activity, which was maximal at physiological pH, 2.5 mM Mg2+, and 2 microM cAMP, was stimulated three-fold over basal levels by cyclic AMP. Addition of calcium or EGTA had no effect on the enzyme activity in the presence or absence of cyclic AMP. Cyclic GMP also did not stimulate endogenous or exogenous protein phosphorylation. Theophylline, an inhibitor of 3',5'-cyclic nucleotide phosphodiesterase activity, increased protein kinase activity in the presence of cyclic AMP. These data show that PNS myelin proteins can be phosphorylated in situ by a protein kinase system whose activity is stimulated selectively by cyclic AMP.
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PMID:Cyclic AMP-stimulated protein kinase activity in rabbit peripheral myelin. 632 73

Apolipoprotein A-I (apo A-I), a soluble lipid transporter, and Po, the major glycoprotein of myelin, are actively synthesized during myelination. To explore the status of post-translational modifications of these proteins in the avian PNS during rapid myelination, endoneurial slices from one day old chick sciatic nerves were incubated with various radioactive precursors that could serve as indicators of such processes. The proteins were isolated from the incubation medium (secreted fraction), the 1% Triton-X-100-soluble intracellular-endoneurial (intracellular) fraction, and myelin-related and purified compact myelin fractions by immunoprecipitation with monospecific anti-apo A-I and or anti-Po antisera. Our results demonstrated that secreted apo A-I is fatty acylated, but not phosphorylated or sulfated. Avian Po protein was phosphorylated by a phorbol ester sensitive protein kinase. Sulfation, as well as fatty acylation, of avian Po protein was observed in organ culture using highly sensitive methods of detection. These results indicate that fatty acylation of secreted apo A-I and phosphorylation, sulfation and fatty acylation of Po have been conserved during evolution, and that these post-translational modifications may play a common function in various species.
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PMID:Post-translational modifications of apolipoprotein A-I and Po proteins in the avian peripheral nerve. 754 97

The best characterized Ca2+ channel modulation in mammalian sympathetic neurons is an inhibition of N-type channels via a pertussis toxin (PTX)-sensitive heterotrimeric G protein. Here, we show that vasoactive intestinal polypeptide (VIP), an abundant neuropeptide in the PNS and CNS, inhibited N-type Ca2+ channels in rat sympathetic neurons in a voltage-dependent, membrane-delimited manner. The effect of VIP was insensitive to PTX but was attenuated by cholera toxin or anti-Gs alpha antibodies. VIP-mediated inhibition was independent of cAMP-dependent protein kinase A (PKA). The results provide evidence for a new signal transduction pathway in which N-type Ca2+ channel modulation requires activation of Gs alpha but is independent of PKA-mediated phosphorylation.
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PMID:VIP inhibits N-type Ca2+ channels of sympathetic neurons via a pertussis toxin-insensitive but cholera toxin-sensitive pathway. 791 96

L1 is an axonal cell adhesion molecule found primarily on projection axons of both the CNS and PNS. It is a phosphorylated membrane-spanning glycoprotein that can be immunoprecipitated from rat brain membranes in association with protein kinase activities. Western blot analysis demonstrates that casein kinase II (CKII), a ubiquitous serine/threonine kinase enriched in brain, is present in these immunoprecipitates. CKII preparations partially purified from PC12 cells are able to phosphorylate recombinant L1 cytoplasmic domain (L1CD), which consists of residues 1,144-1,257. Using these as well as more highly purified kinase preparations, phosphorylation assays of small peptides derived from the L1CD were performed. CKII was able to phosphorylate a peptide encompassing amino acids (aa) 1,173-1,185, as well as a related peptide representing an alternatively spliced nonneuronal L1 isoform that lacks aa 1,177-1,180. Both peptides were phosphorylated with similar kinetic profiles. Serine to alanine substitutions in these peptides indicate that the CKII phosphorylation site is at Ser1,181. This is consistent with experiments in which L1CD was phosphorylated by these kinase preparations, digested, and the radiolabeled fragments sequenced. Furthermore, when L1 immunoprecipitates were used to phosphorylate L1CD, one of the residues phosphorylated is the same residue phosphorylated by CKII. Finally, in vivo radiolabeling indicates that Ser1,181 is phosphorylated in newborn rat brain. These data show that CKII is associated with and able to phosphorylate L1. This phosphorylation may be important in regulating certain aspects of L1 function, such as adhesivity or signal transduction.
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PMID:Casein kinase II phosphorylates the neural cell adhesion molecule L1. 859 52

To investigate the cellular mechanisms regulating neurofilament-heavy subunit (NF-H) side-arm phosphorylation, we studied the ability of three putative neurofilament kinases, glycogen synthase kinase-3 (GSK-3)alpha, GSK-3 beta, and cyclin-dependent kinase-5 (cdk-5), to phosphorylate NF-H in transfected cells. We analysed NF-H phosphorylation by using a panel of phosphorylation-dependent antibodies and also by monitoring the electrophoretic mobility of the transfected NF-H on sodium dodecyl sulphate-polyacrylamide gel electrophoresis because this is known to be affected by side-arm phosphorylation. Our results demonstrate that whereas GSK-3 alpha, GSK-3 beta, and cdk-5 will all phosphorylate NF-H, they generate different antibody reactivity profiles. GSK-3 alpha and GSK-3 beta induce a partial retardation of a proportion of the transfected NF-H, but only cdk-5 alters the rate of electrophoretic migration to that of NF-H from brain. We conclude that cdk-5 and GSK-3 phosphorylate different residues or sets of residues within NF-H sidearm in cells. We further show that cdk-5 is active in both the CNS and the PNS but that this activity is not dependent on expression of its activator, p35. This suggests that there are other activators of cdk-5.
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PMID:Differential cellular phosphorylation of neurofilament heavy side-arms by glycogen synthase kinase-3 and cyclin-dependent kinase-5. 862 28

Previous studies have indicated that certain members of the cyclin-dependent kinase/mitogen-activated protein kinase superfamily are involved in apoptosis of neuronal cells. Here, we have examined programmed cell death induced by withdrawal of neurotrophic support from CNS (rat retinal) and PNS (chick sympathetic, sensory, and ciliary) neurons. All four neuron types were equally rescued by the purine analogues olomoucine and roscovitine. Olomoucine inhibits multiple cyclin-dependent and mitogen-activated protein kinases with similar potency. Roscovitine is a more selective cyclin-dependent kinase inhibitor; but, so is butyrolactone I, which did not prevent retinal ganglion cell death. The specific p38MAPK inhibitor SB-203580 did not prevent apoptosis in retinal ganglion cells. Death of these cells in the absence of neurotrophic factors was accompanied by morphological changes indicative of apoptosis, including nuclear condensation and fragmentation. Treatment with olomoucine or roscovitine not only prevented these apoptotic changes in retinal ganglion cells but also blocked neurite outgrowth. The survival-promoting activity of olomoucine correlated with its in vitro IC50 for c-Jun N-terminal kinase-1 and its potency to repress c-jun induction in live PC12 cells. Roscovitine was more potent in rescuing neurons than in inhibiting Jun kinase. Thus, the antiapoptotic action of roscovitine might be due to inhibition of additional kinases.
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PMID:Apoptosis of central and peripheral neurons can be prevented with cyclin-dependent kinase/mitogen-activated protein kinase inhibitors. 952 56


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