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)

Using polyclonal antibodies we have studied the distribution of protein kinase C in fetal mouse low thoracic vertebrae. By means of a pan protein kinase C antiserum recognizing the catalytic domain of the enzyme, we show that protein kinase C is markedly expressed in chondrocytes before birth. The enzyme seems to be very abundant in the more mature cells that are close to ossification centres as well as the periphery of the intervertebral disc, although it can also be detected in chondrocytes. In order to establish which protein kinase C isoenzyme(s) the chondrocytes produce, we employed polyclonal isoenzyme-specific antisera developed against three calcium-dependent isoforms (alpha, beta, gamma) and three calcium-independent isoforms (delta, epsilon, zeta). Secondary antibody conjugated to alkaline phosphatase revealed that chondrocytes markedly express the beta-isoform. Cells were also weakly stained by the anti-epsilon serum. The immunostaining was completely abolished by pre-incubating primary antibodies with the peptide antigens to which they were raised. These results suggest that protein kinase C (and particularly the beta isoform) could play an important role in mouse fetal chondrogenesis of the vertebral column.
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PMID:An immunohistochemical study of protein kinase C distribution in fetal mouse vertebral column. 798 11

1. Bone resorptive factors, prostaglandin E2 and parathyroid hormone are shown to suppress alkaline phosphatase activity in a rat osteoblastic cell line. 2. Phorbol myristate acetate, but not dibutyryl cAMP or calcium ionophore can suppress alkaline phosphatase activity. 3. The protein kinase C inhibitors (H89, staurosporine) are able to block the suppression of alkaline phosphatase activity induced by prostaglandin E2 and parathyroid hormone. 4. These data suggest that protein kinase C is involved in the inhibition of alkaline phosphatase activity induced by prostaglandin E2 and parathyroid hormone.
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PMID:Prostaglandin E2/parathyroid hormone-induced suppression of alkaline phosphatase activity is mediated by protein kinase C. 800 49

P1 protamines isolated from ejaculated human, stallion, bull, boar and ram spermatozoa and P2 protamines from human and stallion spermatozoa were subjected, after alkaline phosphatase treatment, to in vitro phosphorylation reactions using cAMP-dependent protein kinase (PKA) and protein kinase C (PKC). All P1 protamines were phosphorylated by PKA, whereas P2 protamines were phosphorylated only by PKC. In addition, human, stallion and boar, but not bull and ram, P1 protamines were phosphorylated by PKC. After phosphoamino acid analysis, the protamines showing positive signals for phosphoserine (P-Ser) were subjected to P-Ser conversion reaction and protein sequencing. Only stallion (St1) and human (HP1) P1 protamines contained P-Ser after PKA phosphorylation, located in the middle region of the molecule, i.e., at Ser29 in St1 and Ser28 in HP1. All other phosphorylated P1 protamines contained only P-Thr, which could not be further localized in the sequence with the present methods. After PKC phosphorylation, the internally located Ser residues in human (ser21) and stallion (Ser29) P1 protamines were phosphorylated and, in boar P1 protamine, only Thr43 was slightly phosphorylated. The N-terminally located Ser residues in P1 protamines, which are known to be phosphorylated in vivo, were not phosphorylated by either kinase, indicating that there must still be other types of protamine kinases in sperm cells responsible for their phosphorylation. Within P2 protamines, HP2 was equally well phosphorylated at all Ser residues in addition to some Thr phosphorylation, whereas, in St2, Ser32 was the main target for PKC phosphorylation in vitro. Collectively, PKC is a good candidate for in vivo phosphorylation of P2 protamines and PKA for phosphorylation of some hydroxyamino acid residues in P1 protamines.
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PMID:P2 protamines are phosphorylated in vitro by protein kinase C, whereas P1 protamines prefer cAMP-dependent protein kinase. A comparative study of five mammalian species. 803 90

Phorbol esters (PDBu) stimulate alpha-secretase cleavage and secretion of the Alzheimer amyloid precursor protein (APP). To determine whether any cytoplasmic residues or sequence motifs mediate the PDBu effect on APP processing, this region of APP was altered by point mutations or deletions. To differentiate the mutated APP from the endogenous APP, the APP751 ectodomain between amino acids 1 and 647 was replaced by a human secreted alkaline phosphatase derivative (SEAP). The resultant fusion protein (SEAP-APP751) was cleaved by alpha-secretase at the same site as full-length APP, and its secretion was stimulated by PDBu at a level similar to APP751. However, PDBu-stimulated secretion of the SEAP-APP751 fusion protein reached its maximum level after 30 min of treatment, while secretion of APP751 reached its maximum after 60 min, suggesting that the APP ectodomain affects the kinetics of APP secretion. Mutation of the cytoplasmic serines to alanines had no effect on the PDBu-stimulated secretion of the SEAP-APP, indicating that protein kinase C (PKC) phosphorylation of the cytoplasmic domain of APP is not important for stimulation of APP secretion. Similarly, deletion of the cytoplasmic domain between amino acids 719 and 751 had no effect on the PDBu-stimulated secretion. However, deletion of amino acids 707-751 resulted in a significant increase in the secretory cleavage of the SEAP-APP707 delta C construct, suggesting that the sequence 707-719 is important for the regulated secretion of APP. Cholera toxin, but not pertussis toxin, reduced the PDBu-induced secretion of APP by more than two-fold, suggesting that the PDBu response may be modulated by a cholera toxin sensitive heterotrimeric G-protein.
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PMID:Study of the phorbol ester effect on Alzheimer amyloid precursor processing: sequence requirements and involvement of a cholera toxin sensitive protein. 805 94

The Fos family of transcription factors, c-Fos, FosB, Fra-1 and Fra-2, are rapidly induced in quiescent fibroblasts following serum or growth factor stimulation. The Fos proteins show distinct patterns of expression during cell growth with only Fra-1 and Fra-2 maintained at significant levels in growing cells, suggesting that the different family members direct unique functions for cell growth. Post-translational modification of Fos proteins has been observed following serum stimulation, which may allow an additional level of regulation. Our studies show that the synthesis and post-translational modification of Fra-1 and Fra-2 in Swiss 3T3 cells is serum-dependent during G1 following the transition from G0 and during asynchronous growth but is serum-independent during S phase and mitosis. Post-translational modification of Fra-1 and Fra-2 causes a significant shift in their gel mobility which is eliminated by alkaline phosphatase treatment. Several kinases can phosphorylate Fra-1 and Fra-2 in vitro, including cAMP-dependent kinase (PKA), protein kinase C (PKC), cyclin-dependent kinase 1-cdc2 (cdc2), and mitogen activated protein (MAP) kinase. From these, MAP kinase is the only one that causes a shift in gel mobility similar to that observed in vivo. One dimensional phosphopeptide maps of Fra-1 and Fra-2 phosphorylated by MAP kinase in vitro are similar to those of in vivo labeled Fra-1 and Fra-2, suggesting that MAP kinase may also phosphorylate Fra-1 and Fra-2 in vivo. We have also determined that phosphorylation of Fra-1 and Fra-2 by MAP kinase increases their DNA binding activity.
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PMID:Regulation of Fra-1 and Fra-2 phosphorylation differs during the cell cycle of fibroblasts and phosphorylation in vitro by MAP kinase affects DNA binding activity. 805 17

The involvement of protein kinase C (PKC), cAMP-dependent protein kinase (PKA), and other phosphorylation mechanisms in the rapid desensitization of the [Ca2+]i response to parathyroid hormone (PTH) stimulation was investigated in osteoblast-like UMR-106 cells. A 5 minute preincubation of the cell suspension with phorbol 12,13-dibutyrate (PDB) decreased the response to PTH in a concentration-dependent manner. 1-Oleoyl-2-acetyl-r-glycerol (OAG) pretreatment likewise decreased the PTH response. Staurosporine, a potent protein kinase inhibitor, completely prevented the desensitization caused by PDB. These PDB and staurosporine effects were also observed in 3 mM EGTA-containing medium ([Ca2+]free < 10(-8) M). A 5 minute pretreatment of cells with 1 microM forskolin had no effect on the calcium response to PTH. Homologous and PDB-induced desensitizations differed in several respects. Staurosporine pretreatment resulted in only a slight restoration of the PTH response under conditions of homologous desensitization. Chronic treatment with phorbol ester prevented the desensitization of the PTH response by acute phorbol treatment but not the homologous desensitization. Both homologous and PDB-induced desensitization were relieved by alkaline phosphatase treatment, consistent with the involvement of phosphorylation in the desensitization. This alkaline phosphatase effect on desensitization was inhibited by L-phenylalanine. These results suggest that PTH receptor homologous desensitization involves phosphorylation process(es) other than or in addition to those of PKC.
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PMID:Studies on the mechanism of desensitization of the parathyroid hormone-stimulated calcium signal in UMR-106 cells: reversal of desensitization by alkaline phosphatase but not by protein kinase C downregulation. 807 54

Epidermal growth factor (EGF) stimulated the phosphorylation of connexin43 (Cx43) in WB cells as evidenced by the formation of multiple immunoreactive Cx43 proteins of higher molecular mass which were abolished by treatment with alkaline phosphatase. Phosphorylation of Cx43 occurred within 10 min of EGF stimulation, was sustained for 1 h, and was associated with almost complete inhibition of gap junctional communication in these cells. EGF-induced phosphorylation and communication inhibition were retained in cells pretreated with phorbol 12-myristate 13-acetate (PMA) to deplete protein kinase C. These results show that the EGF inhibition of communication is tightly linked to protein kinase C-independent phosphorylation of Cx43. Further, Cx43 phosphorylated in the presence of EGF did not react with phosphotyrosine antibodies and in 32Pi incorporation experiments was shown to contain only phosphoserine indicating that the tyrosine kinase activity of the EGF receptor was not directly involved.
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PMID:Epidermal growth factor inhibits gap junctional communication and stimulates serine-phosphorylation of connexin43 in WB cells by a protein kinase C-independent mechanism. 808 76

Resistance of tumor cells to doxorubicin is a multifactorial phenomenon. In the present investigation, the ability of resistance modifiers against different resistance mechanisms was analysed. Substances which block P-glycoprotein (P-170) function circumvented resistance of doxorubicin-resistant sarcoma 180 (S180) cells completely (verapamil, thioridazine) or partially (hycanthone), whereas inhibitors of glutathione S-transferase (ethacrynic acid, N-ethylmaleimide, buthionine sulfoximine), and protein kinase C (staurosporine, acridine orange) caused only a partial reversion of resistance. In contrast, an inhibitor of alkaline phosphatase (levamisole) did not overcome doxorubicin-resistance. These results indicate that P-glycoprotein blockers might be more effective to modulate doxorubicin-resistance of S180 cells as compared to other modifiers. Further investigations using other MDR cell lines are required to clarify the generality of these findings.
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PMID:Reversal of doxorubicin-resistance in sarcoma 180 tumor cells by inhibition of different resistance mechanisms. 810 93

The present study was performed to characterize the participation of parathyroid hormone (PTH)- and PTH-related peptide (PTHrP)-responsive dual signal transduction systems [cAMP-dependent protein kinase (PKA) and Calcium/protein kinase C (Ca/PKC)] in the regulation of alkaline phosphatase (ALP) activity in osteoblastic osteosarcoma cells (UMR-106). Both human (h) PTH-(1-34) and hPTHrP-(1-34) at 10(-8) M stimulated ALP activity to the similar degree. Dibutyryl, cAMP (dbcAMP) (10(-5), 10(-4) M) and Sp-diastereoisomer of adenosine cyclic 3',5'-phosphorothioate (Sp-cAMPS), a direct stimulator of PKA (10(-4) M) also stimulated its activity. Phorbol 12-myristate 13-acetate (PMA), an activator of PKC, (10(-7), 10(-6) M) did not affect its activity, while calcium ionophores, A23187 and ionomycin (10(-7), 10(-6) M) inhibited it. Although Rp-diastereoisomer of adenosine cyclic 3',5'-phosphorothioate (Rp-cAMPS), a direct inhibitor of PKA, (10(-4) M) did not affect ALP activity by itself, it significantly antagonized not only Sp-cAMPS-induced increase in ALP activity, but also PTH- and PTHrP-induced one. The present study first indicated that the activation of PKA was directly involved and acted as a main pathway in the regulation of ALP activity by PTH and PTHrP in osteoblasts.
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PMID:Direct involvement of cAMP-dependent protein kinase in the regulation of alkaline phosphatase activity by parathyroid hormone (PTH) and PTH-related peptide in osteoblastic UMR-106 cells. 812 23

The differentiation of HL-60 promyelocytic cells toward mature granulocytic cells induced by dimethyl sulfoxide (DMSO) was accompanied by a quantitative similar increase in alkaline phosphatase (ALP) activity and decrease in protein kinase C (PKC) activity. The combination of DMSO and sphinganine (SP), a potent inhibitor of PKC, increased in parallel the percentage of mature cells and the ALP activity. The enhancement of DMSO-induced differentiation and the potentiation of the decrease of PKC activity by SP also seemed to correlate with each other. Our results indicate that both ALP and PKC may play a role in the DMSO-induced granulocytic differentiation.
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PMID:Sphinganine potentiation of dimethyl sulfoxide-induced granulocyte differentiation, increase of alkaline phosphatase activity and decrease of protein kinase C activity in a human leukemia cell line (HL-60). 813 36


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