Protein kinase Cβ expression in melanoma cells and melanocytes: differential expression correlates with biological responses to 12-O-tetradecanoylphorbol 13-acetate

Powell, Marianne Broome; Rosenberg, Richard K.; Graham, Mark; Birch, Mary; Yamanishi, Douglas T.; Buckmeier, Julie A.; Meyskens, Frank L.

doi:10.1007/bf01624431

Cited by 26 publications

(15 citation statements)

References 35 publications

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“…EP 1 and EP 3 polyclonal antibodies were purchased from Cayman Chemicals (Ann Arbor, MI); monoclonal antibodies to phospho-PKC ζ/λ and to PKCζ were purchased from Cell Signaling Technology (Beverly, MA). Our previous work established that melanoyctes do not express the λ isoform of PKC, consistent with prior reports [19,20], and therefore the phospho-PKC ζ/λ antibody used in the present study only detects phospho-PKCζ in melanocytes [21]. Streptavidin-horse radish peroxidase, biotin-conjugated goat anti-rabbit and goat anti-mouse antibodies, amino-ethyl carbizol (AEC) and 3,3′-diaminobenzidine (DAB) were obtained from Vector Laboratories (Burlingame, CA).…”

Section: Reagentssupporting

confidence: 91%

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Prostaglandin E2 regulates melanocyte dendrite formation through activation of PKCζ

Scott

Fricke

Fender

et al. 2007

Experimental Cell Research

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Prostaglandins are lipid signaling intermediates released by keratinocytes in response to ultraviolet irradiation (UVR) in the skin. The main prostaglandin released following UVR is PGE 2 , a ligand for 4 related G-protein coupled receptors (EP 1 , EP 2 , EP 3 and EP 4 ). Our previous work established that PGE 2 stimulates melanocyte dendrite formation through activation of the EP 1 and EP 3 receptors. The purpose of the present report is to define the signaling intermediates involved in EP 1 and EP 3 -dependent dendrite formation in human melanocytes. We recently showed that activation of the atypical PKCζ isoform stimulates melanocyte dendricity in response to treatment with lysophosphatidylcholine. We therefore examined the potential contribution of PKCζ activation on EP 1 and EP 3 -dependent dendrite formation in melanocytes. Stimulation of the EP 1 and EP 3 receptors by selective agonists activated PKCζ, and inhibition of PKCζ activation abrogated EP 1 and EP 3 -receptor mediated melanocyte dendricity. Because of the importance of Rho-GTP binding proteins in the regulation of melanocyte dendricity, we also examined the effect of EP 1 and EP 3 receptor activation on Rac and Rho activity. Neither Rac nor Rho was activated upon treatment with EP 1,3 -receptor agonists. We show that melanocytes express only the EP 3A1 isoform, but not the EP 3B receptor isoform, previously associated with Rho activation, consistent with a lack of Rho stimulation by EP 3 agonists. Our data suggest that PKCζ activation plays a predominant role in regulation of PGE 2 -dependent melanocyte dendricity.

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Section: Reagentssupporting

confidence: 91%

“…Other important determinants of cytoskeletal remodeling in human melanocytes are the protein kinase C (PKC) signaling pathway [18]. Human melanocytes express α, β, δ, ε and ζ PKC isoforms [19,20]. We recently showed that the atypical PKC isoform PKCζ is a signaling intermediate for melanocyte dendrite formation [21].…”

Section: Introductionmentioning

confidence: 99%

Prostaglandin E2 regulates melanocyte dendrite formation through activation of PKCζ

Scott

Fricke

Fender

et al. 2007

Experimental Cell Research

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“…An alternative explanation is that metastatic melanoma cells fail to respond to TPA secondary to abnormalities of PKC activation. In a prior study, we observed that TPA, a traditional tumor promoter, was not mitogenic for melanoma cells (19) and that there was a decreased expression level of PKCb in metastatic melanoma cells (20), which is required for TPAinduced ROS production. PKCb-deficient human HL-525 cells are also resistant to TPA-induced differentiation with attenuated expression of c-Fos, c-Jun and JunB (21).…”

Section: Primary Metastatic C-junmentioning

confidence: 93%

During Human Melanoma Progression AP‐1 Binding Pairs are Altered with Loss of c‐Jun In Vitro

Yang

McNulty

Meyskens

2004

Pigment Cell Research

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We demonstrated previously that c‐Jun, JunB and c‐Fos RNA were dysregulated in metastatic melanoma cells compared with normal human melanocytes. The purpose of this study was to evaluate the distribution in composition of AP‐1 dimers in human melanoma pathogenesis. We investigated AP‐1 dimer pairing in radial growth phase‐like (RGP) (w3211) and vertical growth phase‐like (VGP) (w1205) human melanoma cells and metastatic cell lines (cloned from patients, c83‐2c, c81‐46A, A375, respectively) compared with melanocytes using electrophoretic mobility shift assay (EMSA), Western blot and transfection analyses. There are progressive variations in AP‐1 composition in different melanoma cell lines compared with normal melanocytes, in which c‐Jun, JunD and FosB were involved in AP‐1 complexes. In w3211, c‐Jun, JunD and Fra‐1 were involved in AP‐1 binding, while in w1205, overall AP‐1 binding activity was decreased significantly and supershift binding was detected only with JunD antibodies. In metastatic c81‐46A and A375 cells, only JunD was involved in AP‐1 binding activity, but in a third (c83‐2c) c‐Jun, JunD and Fra‐1 were present. Western blot evaluation detected c‐Jun in melanocytes and w3211, but this component was decreased significantly or was not detectable in w1205, c81‐46A and A375 cells. In contrast, JunD protein was elevated in c81‐46A and c83‐2c cells compared with melanocytes and RGP and VGP cell lines. Normal melanocytes and c83‐2c cells (which have c‐Jun involved in AP‐1 binding), transfected with c‐Jun antisense and treated with cisplatin, showed higher viability compared with untransfected cells, while in c81‐46A cells (in which only JunD is detectable) no change in cell viability was observed following treatment with cisplatin and c‐jun antisense transfection. A dominant‐negative c‐Jun mutant (TAM67) significantly increased the soft agar colony formation of w3211 and c83‐2c cells. These results suggest that components of AP‐1, especially c‐Jun, may offer a new target for the prevention or treatment of human melanoma progression.

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“…In addition, PKCb expression is reduced or undetectable in 90% of melanoma cell lines and 50% of benign nevi and melanomas (Gilhooly et al, 2001;Oka et al, 1996Oka et al, , 2006Powell et al, 1993;Ryu et al, 2007;Voris et al, 2010;Yamanishi et al, 1991). The function of PKCb in melanin biosynthesis is linked to its ability to phosphorylate and activate tyrosinase, the rate-limiting enzyme in melanin production (Park et al, 1999(Park et al, , 2004b.…”

Section: Tumor Suppressive Protein Kinase C Signalingmentioning

confidence: 99%

“…The general observation that PKC activation inhibits the growth of melanoma cells while stimulating proliferation of normal melanocytes suggests an inherent therapeutic window for selectively targeting transformed melanocytes with PKC agonists (Arita et al, 1994;Cozzi et al, 2006;Eisinger et al, 1983;Eisinger and Marko, 1982;Mason et al, 2009;Pittelkow and Shipley, 1989;Powell et al, 1993;Staudt et al, 2008). The growth inhibitory effects of PKC activation are likely due to some PKC enzymes having tumor suppressive functions in melanoma.…”

Section: Protein Kinase C Activators As Therapeutics For Melanomamentioning

confidence: 99%

Specifying protein kinase C functions in melanoma

Denning

2012

Pigment Cell Melanoma Res

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SummaryThe protein kinase C (PKC) family of serine/threonine protein kinases is a heterogeneous group of enzymes receiving and integrating signals involved in both normal melanocyte biology and melanoma pathology. Alterations in PKC enzyme expression and activation contribute to the malignant phenotype of melanoma in both oncogenic and tumor suppressive roles. Delineating the diverse and often context‐dependent functions of PKC enzymes in melanocyte/melanoma biology is key to capitalize on these kinases as drug targets. This review summarizes several of the diverse functions of PKC in melanocyte and melanoma biology with a focus on PKC enzyme regulation and function.

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Protein kinase Cβ expression in melanoma cells and melanocytes: differential expression correlates with biological responses to 12-O-tetradecanoylphorbol 13-acetate

Cited by 26 publications

References 35 publications

Prostaglandin E2 regulates melanocyte dendrite formation through activation of PKCζ

Prostaglandin E2 regulates melanocyte dendrite formation through activation of PKCζ

During Human Melanoma Progression AP‐1 Binding Pairs are Altered with Loss of c‐Jun In Vitro

Specifying protein kinase C functions in melanoma

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