α-Melanocyte-stimulating hormone stimulates protein kinase C activity in murine B16 melanoma

Abstract

The effect of alpha-melanocyte-stimulating hormone (alpha-MSH) on protein kinase C activity and distribution was investigated in murine B16 F1 melanoma cells. alpha-MSH was found to induce an increased association of protein kinase C (PKC) activity with the particulate fraction of the cells, with an associated loss of enzyme activity from the soluble fraction. The peak response to alpha-MSH occurred between 20 and 60 min of incubation time, and enzyme activities redistributed to those seen in the control cells over the following 12 to 24 h. The average response to alpha-MSH (1 nmol/l) was an approximate 2.5-fold increase in the percentage of enzyme activity associated with the membrane within 1 h of exposure to alpha-MSH; the particulate enzyme activity represented 19.2 +/- 4.4% of total activity in the absence of alpha-MSH and 50.7 +/- 4.7% (means +/- S.E.M., n = 9, P less than 0.005) in the presence of alpha-MSH (1 nmol/l). Cells which had a relatively small percentage of their PKC activity on the membrane initially were significantly (P less than 0.01) more responsive to alpha-MSH stimulation than cells which initially had a relatively large percentage of PKC activity on the membrane. The association of PKC activity with the membrane showed some evidence of being dose-related to alpha-MSH. This is the first report, to the best of our knowledge, of alpha-MSH activating PKC.

Anti-inflammatory and anti-invasive effects of α-melanocyte-stimulating hormone in human melanoma cells

“…Submicromolar concentrations of calcium were shown to be required for optimal a-MSHstimulated cAMP production; slightly higher micromolar concentrations led to inhibition of adenylate cyclase (Mac Neil et al, 1984) and activation of calcium/calmodulin phosphodiesterase, resulting in cAMP breakdown in murine melanoma cells. In these same cells, a-MSH was also demonstrated to activate protein kinase C (Buffey et al, 1992). Although a-MSH may activate the phospholipase C signalling pathway (resulting in increased inositol phosphates, intracellular calcium and activation of protein kinase C) in addition to activating the adenylate cyclase cAMP signalling pathway, the overwhelming evidence from the literature (as reviewed in Eberle, 1988) points to the majority of the actions of a-MSH being mediated by cAMP.…”

“…Although a-MSH may activate the phospholipase C signalling pathway (resulting in increased inositol phosphates, intracellular calcium and activation of protein kinase C) in addition to activating the adenylate cyclase cAMP signalling pathway, the overwhelming evidence from the literature (as reviewed in Eberle, 1988) points to the majority of the actions of a-MSH being mediated by cAMP. The relevance of the dual signalling remains unclear although the calcium signal can modify the cAMP-mediated actions of a-MSH on melanogenesis (Buffey et al, 1992). The simplest hypothesis to explain dual signalling is that most actions of the a-MSH-induced phospholipase C signalling are explained by it suppressing the a-MSH-induced cAMP signal (as proposed in Mac Neil et al, 1984).…”

α-Melanocyte Stimulating Hormone Acts as a Selective Inducer of Secretory Functions in Human Mast Cells

“…As an alternative explanation, MC-receptors might be expressed at only low levels in mast cells or the histamine releasing effect of ␣-MSH could be linked to a non-cAMP mediated signal transduction pathway. Thus, the activation of various post-receptor signaling systems such as those involving inositol triphosphate (IP 3 ), mobilization of intracellular calcium or the JAK/STAT pathway have been described in the past (4,(12)(13)(14). Analysis of possibly involved transcription factors in unstimulated and ␣-MSH-treated cells gave, however, also no indication for ␣-MSH-induced postreceptor signaling events.…”

α-Melanocyte-Stimulating Hormone, MSH 11–13 KPV and Adrenocorticotropic Hormone Signalling in Human Keratinocyte Cells

“…a-MSH is also reported to act via the p38 MAP kinase pathway promoting melanogenesis and inhibiting growth in melanoma cells (Smalley and Eisen, 2000) and also activation of the STAT1 transcription factor (Buggy, 1998). We have previously reported that a-MSH can cause activation of protein kinase C (PKC) in melanoma cells in vitro (Buffey et al, 1992) and can also induce acute intracellular calcium release (MacNeil et al, 1990). As the signalling mechanism of key MSH/ACTH peptides in skin cells is incomplete the objective of this study was to investigate whether human keratinocytes could respond to a-MSH, the MSH 11-13 tripeptides (KPV and KP-D-V), and the ACTH peptides (ACTH 1-39 and ACTH 1-17) with elevation of cAMP or intracellular calcium, and in B16F10C1 mouse melanoma cells with activation of dopa oxidase.…”