Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There have been many studies to determine extrinsic factors that may regulate the neuronal migration and growth of axons and dendrites. However, the intracellular mechanism, especially the regulation of cytoskeleton, has not been clarified. It has been reported that actin filament crosslinking protein, MAR-CKS, play roles in cell motility through cytoskeletal rearrangement accompanied by rapid, PKC-dependent phosphorylation. Recently, we have demonstrated that neuron-specific actin binding protein, drebrin, changed the stability and distribution of microfilaments within the fibroblast and formed highly-branched dendrite-like cell processes from their cell perimeters. It has also been reported that overexpression of microtubule associated protein, tau, in a fibroblast induced long axon-like cellular processes. This review will focus on dynamic regulations of the microfilament by drebrin and those of the microtubules by MAP2 and tau. Since all kinds of cytoskeletons are related to each other, the binding ability of neurofilament H to microtubules and that of MAP2 to neurofilaments were also discussed.
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PMID:[The role of neuronal cytoskeleton associated proteins in neuronal network formation]. 148

Changes in the phosphorylation of three high molecular weight cytoskeletal proteins in platelets (actin binding protein, platelet talin and myosin heavy chain) were investigated after treatment with a phorbol ester. All three showed rapid increases in phosphate incorporation, reaching near-maximal values within three minutes. Phosphopeptide maps of the proteins before and after phorbol treatment revealed a single new site in myosin heavy chain, two new peptides in actin binding protein, and multiple sites in talin. These results point to multiple cytoskeletal targets of protein kinase C and suggest complex mechanisms for reorganizing microfilaments.
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PMID:Phosphorylation of high molecular weight proteins in platelets treated with 12-O-tetradecanoylphorbol-13-acetate. 234 2

Platelet actin binding protein (ABP) as isolated from human platelets exists in at least four phosphorylated forms which we have designated ABP-0, ABP-1, ABP-2, and ABP-3 whose phosphate content ranges from 18 (ABP-0) to 40 (ABP-3) moles Pi/mole ABP. These forms differ in their resistance to calpain cleavage and ability to cross-link F-actin with ABP-3 being the best in each of these properties. Attempts to phosphorylate ABP-1, two or three with protein kinase C (PKC) were unsuccessful except if the proteins were pretreated with Escherichia coli alkaline phosphatase. All of the forms could be phosphorylated with cAMP-dependent kinase (PKA) and subsequent resistance to calpain cleavage conferred. Phosphorylation/dephosphorylation of ABP may be an important regulatory mechanism by which the cytoskeletal architecture is stabilized or transformed.
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PMID:Existence of multiple phosphorylated forms of human platelet actin binding protein. 786 35

The ras-related protein Rho p21 regulates various actin-dependent functions, including smooth muscle contraction. However, the precise mechanism of action of Rho p21 is still not clear. We report here that Rho A is a key regulator of agonist-induced contractile effects in rabbit colonic smooth muscle. Endothelin-1 and C2 ceramide were used. Both seem to activate phosphoinositide 3-kinase (PI 3-kinase) through G protein and pp60(src), respectively. Immunoprecipitation and immunoblotting revealed one form of 21-kDa Rho A that translocated from the cytosol to the membrane in response to stimulation by either endothelin (10(-7) M) or ceramide (10(-7) M) ( approximately 30% increase at 30 s that was sustained at 4 min). The translocation of Rho A to the membrane was confirmed by immunostaining. The translocation of Rho A was inhibited by Clostridium botulinum C3 exoenzyme, which ADP ribosylated Rho A, but was not inhibited by the pp60(src) inhibitor herbimycin A or by the protein kinase C (PKC) inhibitor calphostin C, suggesting that Rho A may be upstream of pp60(src) and PKC or may belong to a different pathway than these proteins. Both ceramide- and endothelin-induced PI 3-kinase activation was inhibited by C3 exoenzyme pretreatment. However, the C3 exoenzyme inhibited endothelin- but not ceramide-induced mitogen-activated protein kinase phosphorylation, indicating that Rho regulates ceramide- and endothelin-induced contraction through different pathways. Furthermore, the dominant negative form of Rho (N19Rho) inhibited the actin binding protein, 27-kDa heat shock protein (HSP27), reorganization in response to ceramide and endothelin observed under confocal microscopy.
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PMID:Rho A regulates sustained smooth muscle contraction through cytoskeletal reorganization of HSP27. 984 84

Transformation of cells by src -like kinases leads to altered cell morphology associated with the disassembly of focal contacts and concomitant increase in tyrosine phosphorylation of pp125(FAK) x p56(lck) is a lymphocyte-specific member of the src family of protein tyrosine kinases that associates with cell surface glycoproteins such as CD4 and CD8. It phosphorylates and activates pp125(FAK) and increases its autokinase activity, thus pretreatment of pp125(FAK) with protein kinase C (PKC) markedly attenuates its phosphorylation and activation, suggesting a potential regulatory pathway of pp125(FAK) activation in focal contacts. p56(lck) further phosphorylates and activates actin binding protein (ABP-280; filamin) and controls its association with cell surface receptors such as beta-2 integrins, actin filament cross-linking, and possibly lipid membrane insertion.
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PMID:p56(lck) Controls phosphorylation of filamin (ABP-280) and regulates focal adhesion kinase (pp125(FAK)). 1217 Oct 35

Caveolin is a principal component of caveolar membranes. In the present study, we utilized a decoy peptide approach to define the degree of involvement of caveolin in PKC-dependent regulation of contractility of differentiated vascular smooth muscle. The primary isoform of caveolin in ferret aorta vascular smooth muscle is caveolin-1. Chemical loading of contractile vascular smooth muscle tissue with a synthetic caveolin-1 scaffolding domain peptide inhibited PKC-dependent increases in contractility induced by a phorbol ester or an alpha agonist. Peptide loading also resulted in a significant inhibition of phorbol ester-induced adducin Ser662 phosphorylation, an intracellular monitor of PKC kinase activity, ERK1/2 activation, and Ser789 phosphorylation of the actin binding protein caldesmon. alpha-Agonist-induced ERK1-1/2 activation was also inhibited by the caveolin-1 peptide. Scrambled peptide-loaded tissues or sham-loaded tissues were unaffected with respect to both contractility and signaling. Depolarization-induced activation of contraction was not affected by caveolin peptide loading. Similar results with respect to contractility and ERK1/2 activation during exposure to the phorbol ester or the alpha-agonist were obtained with the cholesterol-depleting agent methyl-beta-cyclodextrin. These results are consistent with a role for caveolin-1 in the coordination of signaling leading to the regulation of contractility of smooth muscle.
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PMID:Caveolin-1 regulates contractility in differentiated vascular smooth muscle. 1296 91

Vasodilator-stimulated phosphoprotein (VASP), an actin binding protein localized to areas of focal contacts, is a substrate for the cyclic adenosine monophosphate/cyclic guanosine monophosphate (cAMP/cGMP)-dependent protein kinases (PKA, PKG). In this study, we show that serum stimulation of vascular smooth muscle cells (SMCs) induces VASP phosphorylation on Ser157, in a mechanism not dependent on PKA or PKG. We tested the possibility that protein kinase C (PKC), a regulator of cytoskeletal function, is involved. PKC inhibition or down-regulation prevented serum-induced phosphorylation of VASP at Ser157 in rat vascular SMCs. Additionally, recombinant PKCalpha directly phosphorylated Ser157 on VASP. In summary, our data support the hypothesis that PKC phosphorylates VASP and mediates serum-induced VASP regulation.
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PMID:Vasodilator-stimulated phosphoprotein is a substrate for protein kinase C. 1470 52

Filamentous actin binding protein neurabin I (NrbI) targets protein phosphatase-1 (PP1) to specific postsynaptic microdomains, exerting critical control over AMPA receptor (AMPAR)-mediated synaptic transmission. NrbI-targeted synaptic PP1, which promotes synaptic depression upon long-term depression (LTD) stimuli, serves to prevent synaptic depression under basal conditions. The present studies investigate this opposite regulation of AMPAR trafficking during basal synaptic transmission and LTD by expressing NrbI or NrbI mutant, which is defective in PP1 binding, in hippocampal slice or neuron cultures. We find that expression of the NrbI mutant to interfere with PP1 targeting dramatically reduces basal synaptic transmission, which is correlated with the reduction in surface expression of AMPA subtype glutamate receptor (GluR) 1 and GluR2 subunits. Biochemical analysis demonstrates that the NrbI mutant selectively increases the phosphorylation of GluR2 at C-terminal consensus PKC site, serine 880, which is known to favor GluR2 interaction with PDZ (postsynaptic density 95/Discs large/zona occludens 1) protein PICK1 (protein interacting with C kinase-1). Inhibition of PKC activity or GluR2-PICK1 interaction completely reverses the synaptic depression in neurons expressing the NrbI mutant, suggesting that NrbI-targeted synaptic PP1 stabilizes the basal transmission by negatively controlling PKC phosphorylation of GluR2 and the subsequent PICK1-mediated decrease in GluR2-containing AMPAR surface expression. Distinct from basal transmission, blocking GluR2-PICK1 interaction or PKC activity produces minimal effects on LTD in NrbI-expressing neurons. Instead, NrbI-targeted PP1 facilitates LTD by dephosphorylating GluR1 at both serine 845 and serine 831, with GluR2 serine 880 phosphorylation unaltered. Our studies thus elucidate that NrbI-targeted PP1, in response to distinct synaptic activities, regulates the synaptic trafficking of specific AMPAR subunits.
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PMID:Differential regulation of AMPA receptor trafficking by neurabin-targeted synaptic protein phosphatase-1 in synaptic transmission and long-term depression in hippocampus. 1746 80

We have previously reported that gelsolin, an actin binding protein, regulates the fibrillization of amyloid-beta protein. We report here that the expression of cytoplasmic gelsolin (cgelsolin) was upregulated in a concentration-dependent manner when SH-SY5Y, PC-12, and HEK-293 cells were subjected to oxidative stress by treatment with hydrogen peroxide (H(2)O(2). Further studies were done to elucidate the mechanism involved in the regulation of c-gelsolin expression in cells. Pretreatment of cells with cycloheximide (an inhibitor of protein synthesis) resulted in significant inhibition of H(2)O(2)induced c-gelsolin expression, suggesting the possible de novo synthesis of c-gelsolin in cells. Staurosporine, a potent inhibitor of a variety of protein kinases including protein kinase C (PKC), also blocked the H(2)O(2)induced expression of cgelsolin. However, both H(2)O(2) and staurosporine activated the mitogen-activated protein kinases (MAPKs), i.e., c-Jun N-terminal kinase, P38, and extracellular signal-regulated kinase. Pretreatment of cells with Calphostin C, an inhibitor of PKC, blocked the upregulation of cgelsolin induced by H(2)O(2), while specific inhibitors of MAPKs had no effect on c-gelsolin expression, suggesting that MAPKs may not be involved in H(2)O(2)mediated upregulation of cgelsolin. On the other hand, phorbol-12-myristate-13-acetate, an activator of PKC, induced the expression of c-gelsolin. Our studies indicate that c-gelsolin is upregulated in cells under oxidative stress, and PKC is involved in its upregulation. It is suggested that activators of PKC that induce gelsolin expression may have therapeutic significance in Alzheimer's disease.
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PMID:Upregulation of cytoplasmic gelsolin, an amyloid-beta-binding protein, under oxidative stress conditions: involvement of protein kinase C. 2015 39

Excitatory amino acid carrier 1 (EAAC1) belongs to the family of the Na(+)-dependent glutamate carriers. Although the association between defective EAAC1 function and neurologic disease has been repeatedly studied, EAAC1 regulation is not yet fully understood. We have reported that in C6 glioma cells both the activity and membrane targeting of EAAC1 require the integrity of actin cytoskeleton. Here we show that, in the same model, EAAC1 partially co-localizes with actin filaments at the level of cell processes. Moreover, perinuclear spots in which EAAC1 co-localizes with the actin binding protein alpha-adducin are observed in some cells and, consistently, faint co-immunoprecipitation bands between EAAC1 and alpha-adducin are detected. Co-localization and partial co-immunoprecipitation of EAAC1 and adducin are still detectable after cell treatment with phorbol esters, a condition that leads to a protein kinase C (PKC)-dependent increase of EAAC1 expression on the membrane and to the phosphorylation of adducin. A co-immunoprecipitation band was also detected in protein extracts of rat hippocampus. The amount of adducin co-immunoprecipitated with EAAC1 increases after the treatment of C6 cells with retinoic acid, a differentiating agent that induces EAAC1 overexpression in this cell model. Moreover, in clones of C6 cells transfected with a hemagglutinin (HA)-tagged adducin, the bands of EAAC1 immunoprecipitated by an anti-HA antiserum were proportional to EAAC1 expression. These results suggest the existence of a pool of EAAC1 transporters associated with the actin binding protein alpha-adducin in a PKC-insensitive manner.
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PMID:The glutamate transporter excitatory amino acid carrier 1 associates with the actin-binding protein alpha-adducin. 2049 42


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