Regulation of protein kinase C and role in cancer biology

Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters.

1982 • 4,786 citations

The molecular heterogeneity of protein kinase C and its implications for cellular regulation

1988 • 4,243 citations

Inositol phosphates and cell signalling

1989 • 4,058 citations

Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer

1993 • 2,282 citations

THE BIOCHEMISTRY OF P-GLYCOPROTEIN-MEDIATED MULTIDRUG RESISTANCE

1989 • 2,060 citations

Early Signals in the Mitogenic Response

1986 • 1,498 citations

Activation of calcium and phospholipid-dependent protein kinase by diacylglycerol, its possible relation to phosphatidylinositol turnover.

1980 • 1,317 citations

Raf-1 activates MAP kinase-kinase

1992 • 1,308 citations

Protein kinase Cα activates RAF-1 by direct phosphorylation

1993 • 1,282 citations

Protein kinase C isoenzymes: divergence in signal transduction?

1993 • 1,237 citations

Phorbol diester receptor copurifies with protein kinase C.

1983 • 1,185 citations

The HL-60 promyelocytic leukemia cell line: proliferation, differentiation, and cellular oncogene expression

1987 • 1,180 citations

Calcium-dependent activation of a multifunctional protein kinase by membrane phospholipids.

1979 • 1,139 citations

SIGNALLING BY RECEPTOR TYROSINE KINASES

1993 • 1,098 citations

Expression of a full-length cDNA for the human "MDR1" gene confers resistance to colchicine, doxorubicin, and vinblastine.

1987 • 1,080 citations

Mammalian multidrug resistance gene: Complete cDNA sequence indicates strong homology to bacterial transport proteins

1986 • 1,058 citations

Hypermutability and mismatch repair deficiency in RER+ tumor cells

1993 • 1,042 citations

Protein Kinase C Contains a Pseudosubstrate Prototope in Its Regulatory Domain

1987 • 1,020 citations

Cell Surface P-Glycoprotein Associated with Multidrug Resistance in Mammalian Cell Lines

1983 • 1,001 citations

Protein kinase C

1991 • 914 citations

The Complete Primary Structure of Protein Kinase C—the Major Phorbol Ester Receptor

1986 • 878 citations

Molecular Pharmacology

1971 • 853 citations

The structure, expression, and properties of additional members of the protein kinase C family.

1988 • 706 citations

Cloning and expression of multiple protein kinase C cDNAs

1986 • 683 citations

Signal Transduction by the Platelet-Derived Growth Factor Receptor

1989 • 653 citations

Epidermal differentiation: the bare essentials.

1990 • 651 citations

Studies on a cyclic nucleotide-independent protein kinase and its proenzyme in mammalian tissues. I. Purification and characterization of an active enzyme from bovine cerebellum.

1977 • 587 citations

Carcinoma of the Colon and Rectum

1962 • 582 citations

Lipid activation of protein kinase C.

1991 • 566 citations

The pathway to signal achievement

1993 • 563 citations

Overexpression of protein kinase C-delta and -epsilon in NIH 3T3 cells induces opposite effects on growth, morphology, anchorage dependence, and tumorigenicity.

1993 • 546 citations

Protein kinase C zeta subspecies from rat brain: its structure, expression, and properties.

1989 • 508 citations

Protein kinase C activation by diacylglycerol second messengers

1986 • 498 citations

Overproduction of protein kinase C causesdisordered growth control in rat fibroblasts

1988 • 492 citations

14-3-3 proteins: a highly conserved, widespread family of eukaryotic proteins

1992 • 483 citations

Activation of protein kinase C by Triton X-100 mixed micelles containing diacylglycerol and phosphatidylserine.

1985 • 471 citations

Limited Proteolysis of Protein Kinase C Subspecies by Calcium-dependent Neutral Protease (Calpain)

1989 • 470 citations

Tissue-specific expression of three distinct types of rabbit protein kinase C

1987 • 469 citations

Inhibition of protein kinase C by tamoxifen.

1985 • 464 citations

Inhibitory action of chlorpromazine, dibucaine, and other phospholipid-interacting drugs on calcium-activated, phospholipid-dependent protein kinase.

1980 • 464 citations

Ras -Transformed Cells: Altered Levels of Phosphatidylinositol-4,5-Bisphosphate and Catabolites

1986 • 450 citations

Tissue and cellular distribution of the extended family of protein kinase C isoenzymes

1992 • 441 citations

A phorbol ester receptor/protein kinase, nPKC eta, a new member of the protein kinase C family predominantly expressed in lung and skin.

1990 • 434 citations

Protein kinase C as the receptor for the phorbol ester tumor promoters: sixth Rhoads memorial award lecture.

1988 • 430 citations

Protein kinase C, calcium and phospholipid degradation

1992 • 400 citations

Allosteric regulation of the epidermal growth factor receptor kinase.

1986 • 381 citations

Purification of the 170- to 180-kilodalton membrane glycoprotein associated with multidrug resistance. 170- to 180-kilodalton membrane glycoprotein is an ATPase.

1988 • 340 citations

Multidrug Resistance1

1988 • 321 citations

Protein kinase C activation by cis-fatty acid in the absence of Ca2+ and phospholipids.

1986 • 309 citations

Inhibition of phorbol ester-dependent differentiation of human promyelocytic leukemic (HL-60) cells by sphinganine and other long-chain bases.

1986 • 307 citations

Vinblastine photoaffinity labeling of a high molecular weight surface membrane glycoprotein specific for multidrug-resistant cells.

1986 • 290 citations

Altered growth regulation and enhanced tumorigenicity of NIH 3T3 fibroblasts transfected with protein kinase C-I cDNA

1988 • 285 citations

Coordinate changes in gene expression which mark the spinous to granular cell transition in epidermis are regulated by protein kinase C.

1993 • 256 citations

Phorbol esters induce multidrug resistance in human breast cancer cells.

1988 • 241 citations

Three distinct forms of rat brain protein kinase C: Differential response to unsaturated fatty acids

1987 • 239 citations

Immunochemical evidence that three protein kinase C isozymes increase in abundance during HL-60 differentiation induced by dimethyl sulfoxide and retinoic acid.

1988 • 239 citations

Diacylglycerols mimic phorbol diester induction of leukemic cell differentiation.

1985 • 234 citations

Protein kinase C phosphorylates topoisomerase II: topoisomerase activation and its possible role in phorbol ester-induced differentiation of HL-60 cells.

1986 • 231 citations

Distinct patterns of expression of different protein kinase C mRNAs in rat tissues

1987 • 227 citations

The epsilon isoform of protein kinase C is an oncogene when overexpressed in rat fibroblasts.

1993 • 222 citations

Protein kinase C activation in mixed micelles. Mechanistic implications of phospholipid, diacylglycerol, and calcium interdependencies.

1986 • 217 citations

Tissue distribution and developmental expression of protein kinase C isozymes.

1988 • 215 citations

Isolation and characterization of PKC-L, a new member of the protein kinase C-related gene family specifically expressed in lung, skin, and heart.

1991 • 212 citations

Elevated protein kinase C expression in human breast tumor biopsies relative to normal breast tissue.

1989 • 211 citations

Multidrug resistance (mdr) genes in human cancer

1991 • 209 citations

The heterogeneity of protein kinase C in various rat tissues

1988 • 208 citations

Platelet-Derived Growth Factor (PDGF)-Dependent Association of Phospholipase C-γ with the PDGF Receptor Signaling Complex

1990 • 204 citations

Protein kinase C isotypes in human erythroleukemia (K562) cell proliferation and differentiation. Evidence that beta II protein kinase C is required for proliferation

1993 • 202 citations

Protein kinase C phosphorylates P-glycoprotein in multidrug resistant human KB carcinoma cells.

1990 • 200 citations

Role of activation of protein kinase C in the stimulation of colonic epithelial proliferation and reactive oxygen formation by bile acids.

1987 • 199 citations

Phosphorylation of the Mr 170,000 to 180,000 glycoprotein specific to multidrug-resistant tumor cells: effects of verapamil, trifluoperazine, and phorbol esters.

1987 • 198 citations

Chronic ethanol exposure increases levels of protein kinase C delta and epsilon and protein kinase C-mediated phosphorylation in cultured neural cells.

1991 • 195 citations

Ca(2+)-independent isoforms of protein kinase C differentially translocate in smooth muscle

1992 • 185 citations

Overexpression of Protein Kinase C in HT29 Colon Cancer Cells Causes Growth Inhibition and Tumor Suppression

1990 • 179 citations

Selective regulation of expression of protein kinase C (PKC) isoenzymes in multidrug-resistant MCF-7 cells. Functional significance of enhanced expression of PKC alpha.

1993 • 166 citations

Independent mechanisms account for the regulation by protein kinase C of the epidermal growth factor receptor affinity and tyrosine-protein kinase activity.

1988 • 161 citations

Biosynthesis and Posttranslational Modifications of Protein Kinase C in Human Breast Cancer Cells

1989 • 160 citations

Expression of four protein kinase C isoforms in rat fibroblasts. Distinct subcellular distribution and regulation by calcium and phorbol esters.

1992 • 160 citations

Transfection with Protein Kinase Cα Confers Increased Multidrug Resistance to MCF-7 Cells Expressing P-Glycoprotein

1991 • 146 citations

The beta isoform of protein kinase C stimulates human melanogenesis by activating tyrosinase in pigment cells

1993 • 145 citations

Expression of protein kinase C genes in hemopoietic cells is cell-type- and B cell-differentiation stage specific.

1991 • 142 citations

Transcriptional regulation of protein kinase C by 1,25-dihydroxyvitamin D3 in HL-60 cells.

1990 • 141 citations

Bryostatins: Potent, new mitogens that mimic phorbol ester tumor promoters

1985 • 140 citations

Molecular Genetic Analysis of the Regulatory and Catalytic Domains of Protein Kinase C

1989 • 138 citations

Multiple isoforms of a protein kinase C inhibitor (KCIP‐1/14‐3‐3) from sheep brain

1992 • 135 citations

Phosphorylation of the multidrug resistance associated glycoprotein

1987 • 131 citations

Regulation of protein kinase C by ionizing radiation.

1990 • 128 citations

Altered levels of protein kinase C and Ca2+-dependent protein kinases in human colon carcinomas.

1987 • 126 citations

Cell Growth and Differentiation

2004 • 124 citations

Lipoxygenase metabolites of arachidonic and linoleic acids modulate the adhesion of tumor cells to endothelium via regulation of protein kinase C.

1991 • 121 citations

Biology of the protein kinase C family

1989 • 120 citations

A mutant protein kinase C that can transform fibroblasts

1989 • 119 citations

Application of phorbol ester to mouse skin causes a rapid and sustained loss of protein kinase C

1987 • 117 citations

Regulation of platelet protein kinase C by oleic acid. Kinetic analysis of allosteric regulation and effects on autophosphorylation, phorbol ester binding, and susceptibility to inhibition.

1990 • 116 citations

Activation of protein kinase C by oleic acid. Determination and analysis of inhibition by detergent micelles and physiologic membranes: requirement for free oleate.

1992 • 112 citations

Overexpression of protein kinase C in HT29 colon cancer cells causes growth inhibition and tumor suppression.

1990 • 112 citations

Regulation by phorbol ester and protein kinase C inhibitors, and by a protein phosphatase inhibitor (okadaic acid), of P-glycoprotein phosphorylation and relationship to drug accumulation in multidrug-resistant human KB cells.

1992 • 111 citations

Transcripts encoding protein kinase C‐α, ‐ϵ, ‐ζ, and ‐ζ are expressed in basal and differentiating mouse keratinocytes in vitro and exhibit quantitative changes in neoplastic cells

1992 • 111 citations

The regulation of protein kinase C by chenodeoxycholate, deoxycholate and several structurally related bile acids

1987 • 110 citations

Protein kinase C isozymes have distinct roles in neural induction and competence in Xenopus

1992 • 110 citations

Increased expression of protein kinase C alpha plays a key role in retinoic acid-induced melanoma differentiation.

1992 • 109 citations

Analysis of P-glycoprotein phosphorylation in HL60 cells isolated for resistance to vincristine.

1991 • 109 citations

Predominant expression of nPKC eta, a Ca(2+)-independent isoform of protein kinase C in epithelial tissues, in association with epithelial differentiation.

1993 • 108 citations

Tumor promoter-induced membrane-bound protein kinase C regulates hematogenous metastasis.

1988 • 107 citations

Selective regulation of protein kinase C isoenzymes by oleic acid in human platelets.

1993 • 106 citations

A phorbol ester binding domain of protein kinase C gamma. Deletion analysis of the Cys2 domain defines a minimal 43-amino acid peptide.

1994 • 105 citations

Cell calcium and the control of membrane transport.

1987 • 101 citations

Cancer metastasis

1991 • 98 citations

Inhibition of Invasion of Invasive Human Bladder Carcinoma Cells by Protein Kinase C Inhibitor Staurosporine

1990 • 94 citations

Elevated level of nuclear protein kinase C in multidrug-resistant MCF-7 human breast carcinoma cells.

1992 • 94 citations

Selective post-transcriptional down-regulation of protein kinase C isoenzymes in leukemic T cells chronically treated with phorbol ester.

1990 • 89 citations

Modulation of drug permeability in chinese hamster ovary cells. Possible role for phosphorylation of surface glycoproteins

1977 • 89 citations

Protein kinase Cζ and n in murine epidermis TPA induces down‐regulation of PKCn but not PKCζ

1992 • 88 citations

Distinct cellular expression of beta I- and beta II-subspecies of protein kinase C in rat cerebellum

1988 • 86 citations

Immunological quantitation of phospholipid/CA²⁺‐dependent protein kinase of human mammary carcinoma cells: Inverse relationship to estrogen receptors

1987 • 86 citations

Platelet-derived growth factor (PDGF)-dependent association of phospholipase C-gamma with the PDGF receptor signaling complex.

1990 • 86 citations

Level of protein kinase C activity correlates directly with resistance to adriamycin in murine fibrosarcoma cells

1989 • 86 citations

Human Multidrug Resistant KB Cells Overexpress Protein Kinase C: Involvement in Drug Resistance

1989 • 82 citations

Expression of the antisense cDNA for protein kinase C alpha attenuates resistance in doxorubicin-resistant MCF-7 breast carcinoma cells.

1993 • 79 citations

Calcium-dependent activation of protein kinase C. The role of the C2 domain in divalent cation selectivity.

1993 • 78 citations

A phorbol ester binding domain of protein kinase C gamma. High affinity binding to a glutathione-S-transferase/Cys2 fusion protein.

1994 • 77 citations

Cellular signaling in thymocyte apoptosis.

1992 • 75 citations

The protein kinase C-related PKC-L(eta) gene product is localized in the cell nucleus.

1992 • 74 citations

Inhibition of MCF-7 cell growth by 12-O-tetradecanoylphorbol-13-acetate and 1,2-dioctanoyl-sn-glycerol: distinct effects on protein kinase C activity.

1988 • 71 citations

Use of a PCR-based method to characterize protein kinase C isoform expression in cardiac cells

1993 • 70 citations

1,25-Dihydroxyvitamin D3 regulation of phorbol ester receptors in HL-60 leukemia cells.

1987 • 70 citations

Failure of wild-type or a mutant form of protein kinase C-α to transform fibroblasts

1991 • 68 citations

Tamoxifen resistance in breast cancer

1993 • 68 citations

Modulation of endothelial cell expression of intercellular adhesion molecule 1 by protein kinase c activation

1989 • 67 citations

Inhibition of protein kinase C by antineoplastic agents: Implications for drug resistance

1987 • 67 citations

Adenocarcinoma of the colon and rectum

1968 • 66 citations

High calcium content of pleiotropic drug-resistant P388 and K562 leukemia and Chinese hamster ovary cells.

1984 • 65 citations

Effects of 12-O-tetradecanoylphorbol-13-acetate on adhesiveness and lung-colonizing ability of Lewis lung carcinoma cells.

1986 • 63 citations

Protein kinase C desensitization by phorbol esters and its impact on growth of human breast cancer cells

1986 • 62 citations

Protein kinase C down-regulation, and not transient activation, correlates with melanocyte growth.

1991 • 62 citations

Cell type-specific expression of the genes for the protein kinase C family: Down regulation of mRNAs for PKCα and nPKCε upon in vitro differentiation of a mouse neuroblastoma cell line Neuro 2a

1989 • 62 citations

Role of protein kinase C in phosphorylation of vinculin in adriamycin-resistant HL-60 leukemia cells.

1988 • 61 citations

Possible involvement of Ca2+ mobilization and protein kinase C activation in the induction of spontaneous metastasis by mouse mammary adenocarcinoma cells.

1989 • 60 citations

Characterization and differential expression of protein kinase C isoforms in PC12 cells Differentiation parallels an increase in PKC beta₁₁

1992 • 60 citations

Expression of four protein kinase C isoforms in rat fibroblasts. Differential alterations in ras-, src-, and fos-transformed cells.

1992 • 58 citations

Nonmutagenic mechanisms in carcinogenesis: role of protein kinase C in signal transduction and growth control.

1991 • 58 citations

Protein kinase C beta gene expression is associated with susceptibility of human promyelocytic leukemia cells to phorbol ester-induced differentiation.

1992 • 56 citations

Protein kinase C-γ is present in adriamycin resistant HL-60 leukemia cells

1990 • 53 citations

In vitro model for intrinsic drug resistance: effects of protein kinase C activators on the chemosensitivity of cultured human colon cancer cells.

1991 • 52 citations

Developmental expression of protein kinase C isozymes in rat cerebellum

1990 • 51 citations

Evidence for increased synthesis as well as increased degradation of protein kinase C after treatment of human osteosarcoma cells with phorbol ester.

1987 • 50 citations

Selective regulation of expression of protein kinase C beta isoenzymes occurs via alternative splicing

1993 • 50 citations

Role of cofactors in protein kinase C activation

1992 • 48 citations

Expression of protein kinase C isoenzymes in thymocyte subpopulations and their differential regulation.

1991 • 46 citations

Phorbol esters inhibit the proliferation of MCF-7 cells

1986 • 45 citations

Protein kinase C mRNA levels and activity in reconstituted normal human epidermis: Relationships to cell differentiation

1992 • 45 citations

Phorbol diester-induced alterations in the expression of protein kinase C isozymes and their mRNAs. Analysis in wild-type and phorbol diester-resistant HL-60 cell clones

1991 • 45 citations

Inhibition of experimental metastasis and cell adhesion of B16F1 melanoma cells by inhibitors of protein kinase C.

1992 • 44 citations

Isolation and Characterization of PKC-L, A New Member of the Protein Kinase C-Related Gene Family Specifically Expressed in Lung, Skin, and Heart

1991 • 44 citations

Transformation by a ras oncogene causes increased expression of protein kinase C-alpha and decreased expression of protein kinase C-epsilon.

1990 • 44 citations

An inhibitor of protein kinase C, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine(H-7) inhibits TPA-induced reduction of vincristine uptake from P388 murine leukemic cell

1986 • 43 citations

Expression of Protein Kinase C Genes during Ontogenic Development of the Central Nervous System

1989 • 43 citations

Protein kinase C isoforms in multidrug resistant P388/ADR cells: a possible role in daunorubicin transport

1992 • 42 citations

Protein kinase C isoenzymes in human neuroblasts involvement of PKCε in cell differentiation

1993 • 41 citations

Growth of melanocytic cells is associated with down-regulation of protein kinase C alpha, delta, and epsilon isoforms. Possible role of diacylglycerol.

1993 • 41 citations

Decreased levels of protein kinase C enzyme activity and protein kinase C mRNA in primary colon tumors

1993 • 40 citations

Fatty acid activation of protein kinase C: Dependence on diacylglycerol

1988 • 39 citations

Expression of protein kinase C genes during ontogenic development of the central nervous system.

1989 • 37 citations

Transient enhancement of multidrug resistance by the bile acid deoxycholate in murine fibrosarcoma cells in vitro

1991 • 37 citations

Specific role for protein kinase C beta in cell differentiation.

1994 • 37 citations

Induction of protein kinase C mRNA in cultured lymphoblastoid T cells by iron-transferrin but not by soluble iron

1991 • 36 citations

Role of protein kinase C in the modulation of multidrug resistance: expression of the atypical gamma isoform of protein kinase C does not confer increased resistance to doxorubicin.

1992 • 34 citations

Protein kinase C: A key factor in the regulation of tumor cell adhesion to the endothelium

1993 • 34 citations

Resistance to phorbol ester-induced differentiation of a U-937 myeloid leukemia cell variant with a signaling defect upstream to Raf-1 kinase.

1993 • 34 citations

Protein kinase C activity and multidrug resistance in MOLT-3 human lymphoblastic leukemia cells resistant to trimetrexate.

1991 • 32 citations

Glutathione S-transferase is an in vitro substrate of Ca++-phospholipid-dependent protein kinase (protein kinase C)

1989 • 32 citations

A novel N-myristylated synthetic octapeptide inhibits protein kinase C activity and partially reverses murine fibrosarcoma cell resistance to Adriamycin

1991 • 31 citations

Regulation of protein kinase C gene expression by retinoic acid in B16 mouse melanoma cells

1992 • 31 citations

Decreased levels of 1,2-sn-diacylglycerol in human colon tumors.

1991 • 28 citations

Protein kinase C (PKC) activation via human leucocyte antigen class II molecules. A novel regulation of PKC activity.

1991 • 28 citations

Stable expression of a cDNA encoding rat brain protein kinase C-beta I confers a multidrug-resistant phenotype on rat fibroblasts.

1992 • 28 citations

The Differential Role of Protein Kinase C Isozyme in the Rapid Induction of Neurofilament Phosphorylation by Nerve Growth Factor and Phorbol Esters in PC12 Cells

1991 • 26 citations

Differential recovery of protein kinase C-α and -ɛ isozymes after long-term phorbol ester treatment in rat renal mesangial cells

1991 • 25 citations

c-myc gene-induced alterations in protein kinase C expression: a possible mechanism facilitating myc-ras gene complementation.

1991 • 23 citations

Decreased phorbol ester receptor and protein kinase C in P388 murine leukemic cells resistant to etoposide.

1987 • 23 citations

Distinct patterns of phorbol ester-induced downregulation of protein kinase C activity in adriamycin-selected multidrug resistant and parental murine fibrosarcoma cells

1991 • 22 citations

Interferon alpha induces protein kinase C-epsilon (PKC-epsilon) gene expression and a 4.7-kb PKC-epsilon-related transcript.

1993 • 21 citations

Protein kinase C and tumor promoters

1989 • 19 citations

Enhanced expression of the β II subspecies of protein kinase C in differentiating erythroleukemia cells

1990 • 18 citations

Localization and developmental expression of a novel protein kinase C δ gene

1992 • 18 citations

Protein kinase C in the rat retina: immunocharacterization of calcium-independent δ, ϵ and ζ isoenzymes

1992 • 17 citations

Protein kinase C isozyme expression in phorbol ester-sensitive and -resistant EL4 thymoma cells.

1991 • 16 citations

Elevated levels of protein kinase C in Y1 cells which express apolipoprotein E decrease basal steroidogenesis by inhibiting expression of P450-cholesterol side chain cleavage mRNA.

1992 • 15 citations

Effects of phorbol esters on doxorubicin transport systems

1988 • 12 citations

Enhancement of protein kinase C in murine lymphokine-activated killer cells by retinoic acid.

1992 • 11 citations

Tumor cell adherence to cultured capillary endothelial cells is promoted by activators of protein kinase C

1991 • 11 citations

The Protein Kinase C-Related PKC-L(η) Gene Product Is Localized in the Cell Nucleus

1992 • 8 citations

Growth of melanocytic cells is associated with down-regulation of protein kinase C α,δ and ε isoforms: Possible role of diacylglycerol

1993 • 7 citations

Mechanism of activation of protein kinase C: role of diacylglycerol and calcium second messengers.

1987 • 6 citations