Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Melanin is specifically produced in melanocytes. The pathway for melanin biosynthesis is regulated by a number of melanocyte-specific proteins, including tyrosinase and tyrosinase-related protein-1 (TRP-1, b locus protein). To understand the regulation of melanogenesis, we examined tyrosinase activities, mRNA levels of tyrosinase and TRP-1, and eumelanin and pheomelanin contents in mouse B16-F1 melanoma cells after they had been treated with some melanotropic reagents. Cholera toxin, alpha-melanocyte-stimulating hormone, and dibutyryl cyclic AMP increased tyrosinase activity and stimulated eumelanin biosynthesis. These reagents elevated intracellular cAMP levels. In contrast, 12-O-tetradecanoylphorbol 13-acetate reduced tyrosinase activity and eumelanin synthesis. In all cases, the mRNA levels of tyrosinase and TRP-1 changed in parallel with tyrosinase activity and eumelanin content. TRP-1 was induced simultaneously with tyrosinase, although its inducibility was lower than that of tyrosinase. These results suggest that the expressions of tyrosinase and TRP-1 genes are coordinately regulated by melanotropic reagents through cAMP-dependent protein kinase and protein kinase C in mouse B16-F1 cells, and that their coordinate expression causes eumelanin biosynthesis.
...
PMID:Eumelanin biosynthesis is regulated by coordinate expression of tyrosinase and tyrosinase-related protein-1 genes. 768 98

Melanogenesis in melanoma cells can be enhanced by psoralens in the absence of UV light. Melanin biosynthesis is regulated by a number of melanocyte-specific proteins, including tyrosinase, DOPAchrome tautomerase (DCT), and tyrosinase-related protein-1 (TRP-1, gp75). To get more insight on the molecular mechanisms involved in psoralens-induced melanogenesis, we determined tyrosinase and DCT activities as well as mRNA and protein levels of tyrosinase, DCT, and TRP-1 in S91 mouse melanoma cells treated by 5-MOP. High concentration of 5-MOP (5 x 10(-5) M) induced a time-dependent increase of tyrosinase activity and melanin content, which was correlated to an increase of both mRNA and protein levels of tyrosinase. These results demonstrate that the 5-MOP stimulation of melanogenesis is related to increased tyrosinase synthesis. In addition, 5-MOP stimulated TRP-1 synthesis and induced a dose-dependent decrease of DCT activity without any modification in the expression of the protein. We explored then the signalling pathways involved in 5-MOP-induced melanogenesis and, particularly, the role of cyclic AMP and protein kinase C (PKC). A small stimulation of cyclic AMP production was observed in presence of 5-MOP. Furthermore, 1-oleoyl-2-acetylglycerol (OAG), a PKC activator, potentiated the 5-MOP stimulation of tyrosinase activity, while calphostin, a specific PKC inhibitor, inhibited the 5-MOP induction of tyrosinase activity. Phorbol-myristate acetate (PMA), described as a strong activator of PKC, inhibited also the effect of 5-MOP when used at long term. Taken together, these results demonstrate that in murine melanoma cells 5-MOP stimulates melanogenesis by increasing activity and synthesis of tyrosinase. Tyrosinase and TRP-1 expression are coordinately regulated by 5-MOP. Furthermore, a negative correlation between melanogenesis and DCT activity was observed under 5-MOP stimulation. At least, PKA and PKC systems appear to play an important role in the melanogenic effect of 5-MOP.
...
PMID:Regulation of melanogenesis induced by 5-methoxypsoralen without ultraviolet light in murine melanoma cells. 785 73

In melanocytes and in melanoma cells, cyclic AMP (cAMP)-elevating agents stimulate melanogenesis and increase the transcription of tyrosinase, the rate-limiting enzyme in melanin synthesis. However, two other enzymes, tyrosinase-related protein 1 (TRP1) and TRP2, are required for a normal melanization process leading to eumelanin synthesis. In B16 melanoma cells, we demonstrated that stimulation of melanogenesis by cAMP-elevating agents results in an increase in tyrosinase, TRP1, and TRP2 expression. cAMP, through a cAMP-dependent protein kinase pathway, stimulates TRP1 and TRP2 promoter activities in both B16 mouse melanoma cells and normal human melanocytes. Regulation of the TRP1 and TRP2 promoters by cAMP involves a M box and an E box. Further, a classical cAMP response element-like motif participates in the cAMP responsiveness of the TRP2 promoter, demonstrating that the TRP2 gene is subjected to different regulatory processes, which could account for its different expression patterns during embryonic development or under specific physiological and pathological conditions. We also found that microphthalmia, a basic helix-loop-helix transcription factor, strongly stimulates the transcriptional activities of the TRP1 and TRP2 promoters, mainly through binding to the M boxes. Additionally, we demonstrated that cAMP increases microphthalmia expression and thereby its binding to TRP1 and TRP2 M boxes. These convergent and compelling results disclose at least a part of the molecular mechanism involved in the regulation of melanogenic gene expression by cAMP and emphasize the pivotal role of microphthalmia in this process.
...
PMID:Different cis-acting elements are involved in the regulation of TRP1 and TRP2 promoter activities by cyclic AMP: pivotal role of M boxes (GTCATGTGCT) and of microphthalmia. 944 65

The polyether toxin, bistratene A, induced morphological and functional differentiation of a human melanoma cell line (MM96E). The cells became blocked at the G2/M transition and elaborated a number of processes. Tyrosinase activity and melanin content were substantially increased. Northern blot analysis showed up-regulation of mRNA for several genes known to be involved in melanin biosynthesis (pmel17, pmel34, and tyrosinase related proteins, TRP-1 and TRP-2). Bistratene A induced the phosphorylation of several proteins as assessed by 2D gel electrophoresis and one of these was identified as stathmin (oncoprotein 18), a cell-cycle regulated phosphoprotein. Bistratene A specifically induced the translocation of protein kinase Cdelta (PKCdelta) from a soluble to a particulate fraction without affecting other isoforms. These results implicate a role for protein kinase Cdelta in the induction of differentiation of this human melanoma cell line.
...
PMID:Stimulation of melanogenesis in a human melanoma cell line by bistratene A. 963 6

The effects of all-trans retinoic acid on the differentiation and proliferation of immature melanocyte precursors were studied. NCC-melb4 cells are an immortal cloned cell line established from mouse neural crest cells using a single-cell cloning method. These cells were positive for tyrosinase-related protein 1, tyrosinase-related protein 2 and KIT, but were negative for tyrosinase and had no dihydroxyphenylalanine reaction. They contained only stage I melanosomes without any melanosomes in more advanced stages. After treatment with all-trans retinoic acid, many of the cells became tyrosinase- and dihydroxyphenylalanine-reaction-positive, changed from polygonal to dendritic in shape, and had stage III to IV melanosomes. These findings indicate that treatment with all-trans retinoic acid induced the differentiation of NCC-melb4 cells. Reverse transcription polymerase chain reaction analysis revealed a marked increase in expression of microphthalmia-associated transcription factor mRNA after all-trans retinoic acid treatment, suggesting that microphthalmia-associated transcription factor may be the key molecule in this event. Enhanced expression of protein kinase Calpha following treatment with all-trans retinoic acid was also demonstrated. The proliferation of NCC-melb4 cells was inhibited by all-trans retinoic acid in a dose-dependent manner. Increased apoptosis after all-trans retinoic acid treatment was observed by electron microscopy, the TUNEL method, DNA fragmentation assay, and flow cytometry. All-trans retinoic acid upregulated caspase-3 and downregulated bcl-2. Electron microscopy showed that apoptotic cells contained melanosomes of advanced stages, suggesting that mature melanocytes may tend to undergo apoptosis after all-trans retinoic acid treatment. This study provides important clues towards understanding the roles and working mechanisms of retinoic acids in melanocyte development and melanogenesis.
...
PMID:All-trans retinoic acid induces differentiation and apoptosis of murine melanocyte precursors with induction of the microphthalmia-associated transcription factor. 1185 73

Sphingosine-1-phosphate (S1P) has emerged as a bioactive lipid modulator that mediates a variety of cell functions. However, the effects of S1P on melanogenesis are not well known. Therefore, we investigated the actions of S1P on melanin synthesis using a spontaneously immortalized mouse melanocyte cell line, Mel-Ab. This study shows that S1P significantly inhibits melanin synthesis in a concentration-dependent manner, and also that the activity of tyrosinase was reduced in S1P-treated cells. In contrast, a specific extracellular signal-regulated protein kinase (ERK) pathway inhibitor, PD98059, increased tyrosinase activity and melanin production, and PD98059 also restored the S1P-induced reduction of tyrosinase activity and pigmentation. In addition, we found that S1P induces the sustained activation of ERK and the subsequent degradation of microphthalmia-associated transcription factor (MITF), which plays a key role in melanogenesis. Thus, we further studied the relationship between the ERK pathway and melanin synthesis. PD98059 was found to prevent the S1P-induced MITF phosphorylation and degradation and to abrogate the S1P-induced downregulation of tyrosinase and of tyrosinase-related protein 1 (TRP1) production. These results indicate that the ERK pathway is potently involved in the melanogenic signaling cascade, and that S1P-induced ERK activation contributes to reduced melanin synthesis via MITF degradation. Therefore, we suggest that S1P reduces melanin synthesis by ERK activation, MITF phosphorylation and degradation, and by the subsequent downregulation of tyrosinase and TRP-1 production.
...
PMID:Sphingosine-1-phosphate decreases melanin synthesis via sustained ERK activation and subsequent MITF degradation. 1266 51

SOX (SRY type HMG box) proteins are transcription factors that are predominantly known for their roles during development. During melanocyte development from the neural crest, SOX10 regulates microphthalmia-associated transcription factor, which controls a set of genes critical for pigment cell development and pigmentation, including dopachrome tautomerase and tyrosinase. We report here that another SOX factor, SOX9, is expressed by melanocytes in neonatal and adult human skin and is up-regulated by UVB exposure. We demonstrate that this regulation is mediated by cAMP and protein kinase. We also show that agouti signal protein, a secreted factor known to decrease pigmentation, down-regulates SOX9 expression. In adult and neonatal melanocytes, SOX9 regulates microphthalmia-associated transcription factor, dopachrome tautomerase, and tyrosinase promoters, leading to an increase in the expression of these key melanogenic proteins and finally to a stimulation of pigmentation. SOX9 completes the complex and tightly regulated process leading to the production of melanin by acting at a very upstream level. This role of SOX9 in pigmentation emphasizes the poorly understood impact of SOX proteins in adult tissues.
...
PMID:SOX9 is a key player in ultraviolet B-induced melanocyte differentiation and pigmentation. 1770 66

In the kidney, many physiological processes of ion transport and cellular proliferation are mediated via cAMP, which classically activates protein kinase A (PKA). Recently, however, two new cAMP targets, the exchange protein directly activated by cAMP (Epac) 1 and 2, were identified, which mediate alternative pathways to PKA. To investigate their renal expression, antibodies specifically recognizing Epac1 and Epac2 were generated and used in rat immunohistochemistry with antibodies recognizing aquaporin-1 (AQP1), Tamm-Horsfall protein, Calbindin-D(28K), and AQP2 to mark proximal tubules (PT)/thin descending limbs of Henle's loop (tDLH), thick ascending limbs of Henle's loop (TAL), distal convoluted tubule/connecting tubule (DCT/CNT), and the collecting duct (CD) principal cells, respectively. Epac1 and Epac2 were expressed at the brush border of PT cells but were absent from tDLH cells. In the TAL, Epac1 and Epac2 were expressed throughout the cells with some confinement toward the apical membrane. In the DCT/CNT, Epac1 was confined to the apical region of the cells, whereas Epac2 was mainly expressed in the apical and basolateral regions. In the CD, a dispersed Epac1 expression was found in intercalated cells only (cortical CD), principal and intercalated cells [outer medullary CD (OMCD)], and mainly AQP2-negative cells in the inner medullary CD (IMCD). In contrast, Epac2 expression was at the apical and basolateral membrane of cortical principal cells, dispersed and apical in the OMCD, and in all cells of the IMCD. A similar distribution for Epac1/2 was found in the human kidney. The observed expression in different tubular segments suggests a major role for Epac 1/2 in tubular transport physiology and cellular proliferation.
...
PMID:Renal expression of exchange protein directly activated by cAMP (Epac) 1 and 2. 1849 99

Melanogenesis is a physiological process that results in the synthesis of melanin pigments, which play a crucial protective role against skin photocarcinogenesis. The present study was designed to determine the effects of 6-benzylaminopurine (6-BAP) on melanogenesis and elucidate the molecular events of melanogenesis induced by 6-BAP. To elucidate the pigmenting effect of 6-BAP and its mechanism, several experiments were performed in B16 melanoma cells. Melanin content, tyrosinase activity, cAMP production, and Western blots for proteins which are involved in melanogenesis were introduced in this study. Melanin content and tyrosinase activity increased in response to treatment with 6-BAP in a concentration-dependent manner. The tyrosinase, TRP-1, TRP-2 and MITF protein levels were found to increase significantly in response to 6-BAP in a time-dependent manner. In addition, Western blot analysis revealed that 6-BAP increased the phosphorylated level of CRE-binding protein. The increased melanin synthesis that was induced by treatment with 6-BAP treatment was reduced significantly in response to co-treatment with H-89 [a protein kinase A (PKA) inhibitor], whereas co-treatment with SB203580 (a p38 MAPK inhibitor) and Ro-32-0432 (a PKC inhibitor) did not attenuate the increase in melanin content levels that was induced by 6-BAP. In a cAMP production assay, 6-BAP did not increase the intracellular cAMP level. These findings suggest that 6-BAP activates PKA via a cAMP-independent pathway and subsequently stimulates melanogenesis by up-regulating MITF and tyrosinase expression.
...
PMID:6-Benzylaminopurine stimulates melanogenesis via cAMP-independent activation of protein kinase A. 1912 6

Melanogenesis is a physiological process that results in the synthesis of melanin pigments, which play a crucial protective role in protection against skin photocarcinogenesis. Phloridzin is a phloretin 2'-glucoside that is found in many parts of the apple tree that reportedly increases tyrosinase activity and melanin contents through inhibition of protein kinase C (PKC) activity in B16 melanoma cells. In this study, we attempted to accurately determine the effects and mechanisms of action of phloridzin on melanogenesis. Specifically, we observed that phloridzin-induced a dose-dependent increase in tyrosinase activity and melanin contents, and that these changes were accompanied by an increase in the levels of tyrosinase and the tyrosinase-related proteins, TRP-1 and TRP-2. Furthermore, the cAMP-dependent protein kinase A (PKA) inhibitor H89 impaired the response of the tyrosinase activity and melanin synthesis to phloridzin. Additionally, phloridzin stimulated cAMP production and phosphorylation of the cAMP-response element binding protein (CREB). Taken together, the results of this study indicate that phloridzin increases tyrosinase gene expression through the cAMP signaling pathway, thereby leading to the stimulation of melanogenesis.
...
PMID:Phloridzin-induced melanogenesis is mediated by the cAMP signaling pathway. 1957 39


1 2 3 4 5 6 Next >>

---