KEGG   PATHWAY: cge04916
Entry
cge04916                    Pathway                                
Name
Melanogenesis - Cricetulus griseus (Chinese hamster)
Description
Cutaneous melanin pigment plays a critical role in camouflage, mimicry, social communication, and protection against harmful effects of solar radiation. Melanogenesis is under complex regulatory control by multiple agents. The most important positive regulator of melanogenesis is the MC1 receptor with its ligands melanocortic peptides. MC1R activates the cyclic AMP (cAMP) response-element binding protein (CREB). Increased expression of MITF and its activation by phosphorylation (P) stimulate the transcription of tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1), and dopachrome tautomerase (DCT), which produce melanin. Melanin synthesis takes place within specialized intracellular organelles named melanosomes. Melanin-containing melanosomes then move from the perinuclear region to the dendrite tips and are transferred to keratinocytes by a still not well-characterized mechanism.
Class
Organismal Systems; Endocrine system
Pathway map
cge04916  Melanogenesis
cge04916

Organism
Cricetulus griseus (Chinese hamster) [GN:cge]
Gene
100756311  Pomc; pro-opiomelanocortin isoform X2 [KO:K05228]
100750676  Asip; agouti-signaling protein isoform X2 [KO:K08725]
100689067  Gnas; guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
103158534  neuroendocrine secretory protein 55 [KO:K04632]
100764561  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
100773811  Adcy2; adenylate cyclase type 2 isoform X2 [KO:K08042] [EC:4.6.1.1]
100770498  Adcy3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
100768998  Adcy4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
100765958  Adcy5; LOW QUALITY PROTEIN: adenylate cyclase type 5 isoform X2 [KO:K08045] [EC:4.6.1.1]
100768368  Adcy6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
100756132  Adcy7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
113837458  adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
100751372  Adcy9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
100768997  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha isoform X2 [KO:K04345] [EC:2.7.11.11]
100767097  Prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X2 [KO:K04345] [EC:2.7.11.11]
100761582  Creb1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
100762192  Creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X2 [KO:K09048]
100771872  Creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X2 [KO:K09048]
100766300  Creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
100774488  Creb3l3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
100772940  Creb3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
100762260  Ep300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
100770451  histone lysine acetyltransferase CREBBP isoform X3 [KO:K04498] [EC:2.3.1.48]
100754846  Mitf; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
100766046  Wnt1; proto-oncogene Wnt-1 [KO:K03209]
100761413  Wnt2b; protein Wnt-2b [KO:K00182]
100752722  Wnt2; protein Wnt-2 [KO:K00182]
100764164  Wnt3a; protein Wnt-3a isoform X2 [KO:K00312]
100774849  proto-oncogene Wnt-3 isoform X2 [KO:K00312]
100769003  Wnt4; protein Wnt-4 isoform X3 [KO:K00408]
100753089  Wnt5a; protein Wnt-5a [KO:K00444]
100753017  Wnt5b; protein Wnt-5b isoform X2 [KO:K00444]
100751289  Wnt6; protein Wnt-6 isoform X2 [KO:K00445]
100772978  Wnt7a; protein Wnt-7a isoform X2 [KO:K00572]
100755799  Wnt7b; protein Wnt-7b isoform X1 [KO:K00572]
100775075  Wnt8b; protein Wnt-8b [KO:K00714]
100752907  Wnt8a; protein Wnt-8a isoform X2 [KO:K00714]
100766088  Wnt9b; protein Wnt-9b isoform X2 [KO:K01064]
100764466  Wnt9a; protein Wnt-9a isoform X2 [KO:K01064]
100770174  Wnt10a; protein Wnt-10a [KO:K01357]
100766340  Wnt10b; protein Wnt-10b [KO:K01357]
100774690  Wnt11; protein Wnt-11 isoform X1 [KO:K01384]
100764115  Wnt16; protein Wnt-16 [KO:K01558]
100766658  Fzd7; frizzled-7 isoform X2 [KO:K02432]
100770917  Fzd1; frizzled-1 isoform X2 [KO:K02432]
100763109  Fzd2; frizzled-2 isoform X2 [KO:K02235]
100751712  Fzd3; frizzled-3 isoform X1 [KO:K02329]
100756296  Fzd4; frizzled-4 [KO:K02354]
100762351  Fzd5; frizzled-5 isoform X2 [KO:K02375]
113834637  frizzled-8 [KO:K02375]
100774509  Fzd6; frizzled-6 isoform X2 [KO:K02376]
100755785  Fzd10; frizzled-10 isoform X2 [KO:K02842]
100761155  Fzd9; frizzled-9 isoform X2 [KO:K02842]
100689069  Gnao1; guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
100689066  Gnaq; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
100770288  Dvl1; segment polarity protein dishevelled homolog DVL-1 isoform X4 [KO:K02353]
100762587  Dvl2; segment polarity protein dishevelled homolog DVL-2 isoform X2 [KO:K02353]
100773535  Dvl3; segment polarity protein dishevelled homolog DVL-3 isoform X2 [KO:K02353]
100760865  Gsk3b; glycogen synthase kinase-3 beta isoform X7 [KO:K03083] [EC:2.7.11.26]
100773307  Ctnnb1; catenin beta-1 [KO:K02105]
100757390  Tcf7; transcription factor 7 isoform X2 [KO:K02620]
100753225  Tcf7l1; transcription factor 7-like 1 isoform X2 [KO:K04490]
100758400  Tcf7l2; transcription factor 7-like 2 isoform X33 [KO:K04491]
100761200  Lef1; lymphoid enhancer-binding factor 1 isoform X3 [KO:K04492]
100752139  Kitlg; kit ligand isoform X1 [KO:K05461]
100751027  Kit; mast/stem cell growth factor receptor Kit isoform X3 [KO:K05091] [EC:2.7.10.1]
100773737  Hras; GTPase HRas isoform X2 [KO:K02833]
100763178  Kras; GTPase KRas isoform X4 [KO:K07827]
113839127  GTPase KRas-like [KO:K07827]
113837935  GTPase KRas-like isoform X2 [KO:K07827]
113837956  GTPase KRas-like [KO:K07827]
113838653  GTPase KRas-like isoform X2 [KO:K07827]
113838692  GTPase KRas-like [KO:K07827]
113838722  GTPase KRas-like isoform X1 [KO:K07827]
113838818  GTPase KRas-like [KO:K07827]
113837633  GTPase KRas-like isoform X1 [KO:K07827]
113838146  GTPase KRas-like isoform X1 [KO:K07827]
113838876  GTPase KRas-like [KO:K07827]
113838228  GTPase KRas-like isoform X1 [KO:K07827]
113839011  GTPase KRas-like [KO:K07827]
100771078  GTPase KRas-like isoform X2 [KO:K07827]
113837960  GTPase KRas-like [KO:K07827]
113838098  GTPase KRas-like [KO:K07827]
113838326  GTPase KRas-like [KO:K07827]
113838417  GTPase KRas-like isoform X1 [KO:K07827]
113838488  GTPase KRas-like [KO:K07827]
113838583  GTPase KRas-like isoform X1 [KO:K07827]
113838676  GTPase KRas-like [KO:K07827]
113838679  GTPase KRas-like isoform X1 [KO:K07827]
113838746  GTPase KRas-like [KO:K07827]
113838796  GTPase KRas-like isoform X1 [KO:K07827]
113838871  GTPase KRas-like [KO:K07827]
113838872  GTPase KRas-like [KO:K07827]
113838892  GTPase KRas-like [KO:K07827]
113838898  GTPase KRas-like [KO:K07827]
113838914  GTPase KRas-like [KO:K07827]
113838921  GTPase KRas-like [KO:K07827]
113838942  GTPase KRas-like isoform X1 [KO:K07827]
113838943  GTPase KRas-like isoform X1 [KO:K07827]
113839007  GTPase HRas-like isoform X1 [KO:K07827]
118239746  GTPase KRas-like isoform X1 [KO:K07827]
118239767  GTPase KRas-like isoform X1 [KO:K07827]
118239768  GTPase KRas-like [KO:K07827]
118239770  GTPase KRas-like [KO:K07827]
118239801  GTPase KRas-like [KO:K07827]
118239825  GTPase KRas-like isoform X1 [KO:K07827]
100757614  Nras; GTPase NRas [KO:K07828]
100769018  Raf1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
100689403  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
113835540  dual specificity mitogen-activated protein kinase kinase 1-like isoform X1 [KO:K04368] [EC:2.7.12.2]
103158537  dual specificity mitogen-activated protein kinase kinase 1-like isoform X2 [KO:K04368] [EC:2.7.12.2]
100774204  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 isoform X2 [KO:K04369] [EC:2.7.12.2]
100759514  Mapk1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
100753149  Mapk3; mitogen-activated protein kinase 3 isoform X2 [KO:K04371] [EC:2.7.11.24]
100752294  tyrosinase isoform X3 [KO:K00505] [EC:1.14.18.1]
100774614  Tyrp1; 5,6-dihydroxyindole-2-carboxylic acid oxidase [KO:K00506] [EC:1.14.18.-]
100764118  Dct; L-dopachrome tautomerase isoform X2 [KO:K01827] [EC:5.3.3.12]
100768493  Edn1; endothelin-1 [KO:K16366]
100762726  Ednrb; endothelin receptor type B [KO:K04198]
100689068  Gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
100689072  Gnai3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
100689070  Gnai1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
100760134  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X2 [KO:K05858] [EC:3.1.4.11]
100760731  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
100770957  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
100751979  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X2 [KO:K05858] [EC:3.1.4.11]
100766751  Calml3; calmodulin-like protein 3 [KO:K02183]
100767046  Calml5; calmodulin-like protein 5 isoform X1 [KO:K02183]
100762749  Calm3; calmodulin-3 isoform X2 [KO:K02183]
100765281  Calm2; calmodulin-2 isoform X2 [KO:K02183]
100771772  Calm1; calmodulin-1 isoform X2 [KO:K02183]
100757500  Calml4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
100751814  calmodulin-like isoform X2 [KO:K02183]
100769205  Camk2b; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X2 [KO:K04515] [EC:2.7.11.17]
100763272  Camk2g; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X2 [KO:K04515] [EC:2.7.11.17]
100752268  calcium/calmodulin-dependent protein kinase type II subunit delta isoform X4 [KO:K04515] [EC:2.7.11.17]
100765253  Camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X3 [KO:K04515] [EC:2.7.11.17]
100766006  Prkca; protein kinase C alpha type isoform X2 [KO:K02677] [EC:2.7.11.13]
100760922  Prkcb; protein kinase C beta type isoform X2 [KO:K19662] [EC:2.7.11.13]
100762950  Prkcg; protein kinase C gamma type isoform X2 [KO:K19663] [EC:2.7.11.13]
Compound
C00076  Calcium cation
C00082  L-Tyrosine
C00165  Diacylglycerol
C00575  3',5'-Cyclic AMP
C01245  D-myo-Inositol 1,4,5-trisphosphate
C05606  Melanin
Reference
PMID:15383650
  Authors
Slominski A, Tobin DJ, Shibahara S, Wortsman J.
  Title
Melanin pigmentation in mammalian skin and its hormonal regulation.
  Journal
Physiol Rev 84:1155-228 (2004)
DOI:10.1152/physrev.00044.2003
Reference
PMID:10841026
  Authors
Busca R, Ballotti R.
  Title
Cyclic AMP a key messenger in the regulation of skin pigmentation.
  Journal
Pigment Cell Res 13:60-9 (2000)
DOI:10.1034/j.1600-0749.2000.130203.x
Reference
PMID:15016298
  Authors
Imokawa G.
  Title
Autocrine and paracrine regulation of melanocytes in human skin and in pigmentary disorders.
  Journal
Pigment Cell Res 17:96-110 (2004)
DOI:10.1111/j.1600-0749.2003.00126.x
Reference
PMID:11023702
  Authors
Wikberg JE, Muceniece R, Mandrika I, Prusis P, Lindblom J, Post C, Skottner A.
  Title
New aspects on the melanocortins and their receptors.
  Journal
Pharmacol Res 42:393-420 (2000)
DOI:10.1006/phrs.2000.0725
Reference
PMID:12894244
  Authors
Chin L.
  Title
The genetics of malignant melanoma: lessons from mouse and man.
  Journal
Nat Rev Cancer 3:559-70 (2003)
DOI:10.1038/nrc1145
Reference
PMID:16822996
  Authors
Miller AJ, Mihm MC Jr.
  Title
Melanoma.
  Journal
N Engl J Med 355:51-65 (2006)
DOI:10.1056/NEJMra052166
Reference
PMID:12753399
  Authors
Saito H, Yasumoto K, Takeda K, Takahashi K, Yamamoto H, Shibahara S.
  Title
Microphthalmia-associated transcription factor in the Wnt signaling pathway.
  Journal
Pigment Cell Res 16:261-5 (2003)
DOI:10.1034/j.1600-0749.2003.00039.x
Reference
PMID:9263329
  Authors
Imokawa G, Kobayashi T, Miyagishi M, Higashi K, Yada Y.
  Title
The role of endothelin-1 in epidermal hyperpigmentation and signaling mechanisms of mitogenesis and melanogenesis.
  Journal
Pigment Cell Res 10:218-28 (1997)
DOI:10.1111/j.1600-0749.1997.tb00488.x
Reference
PMID:10643996
  Authors
Park HY, Gilchrest BA.
  Title
Signaling pathways mediating melanogenesis.
  Journal
Cell Mol Biol (Noisy-le-grand) 45:919-30 (1999)
Reference
PMID:10347209
  Authors
Park HY, Perez JM, Laursen R, Hara M, Gilchrest BA.
  Title
Protein kinase C-beta activates tyrosinase by phosphorylating serine residues in its cytoplasmic domain.
  Journal
J Biol Chem 274:16470-8 (1999)
DOI:10.1074/jbc.274.23.16470
Reference
PMID:11602344
  Authors
Sturm RA, Teasdale RD, Box NF.
  Title
Human pigmentation genes: identification, structure and consequences of polymorphic variation.
  Journal
Gene 277:49-62 (2001)
DOI:10.1016/S0378-1119(01)00694-1
Reference
PMID:11041354
  Authors
Hearing VJ.
  Title
The melanosome: the perfect model for cellular responses to the environment.
  Journal
Pigment Cell Res 13 Suppl 8:23-34 (2000)
DOI:10.1034/j.1600-0749.13.s8.7.x
Reference
PMID:16246839
  Authors
Molina DM, Grewal S, Bardwell L.
  Title
Characterization of an ERK-binding domain in microphthalmia-associated transcription factor and differential inhibition of ERK2-mediated substrate phosphorylation.
  Journal
J Biol Chem 280:42051-60 (2005)
DOI:10.1074/jbc.M510590200
Related
pathway
cge00350  Tyrosine metabolism
cge04010  MAPK signaling pathway
cge04310  Wnt signaling pathway
cge05218  Melanoma
KO pathway
ko04916   
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