KEGG   PATHWAY: mcal04916
Entry
mcal04916                   Pathway                                
Name
Melanogenesis - Mus caroli (Ryukyu mouse)
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
mcal04916  Melanogenesis
mcal04916

Organism
Mus caroli (Ryukyu mouse) [GN:mcal]
Gene
110307137  Pomc; pro-opiomelanocortin [KO:K05228]
110290460  Asip; agouti-signaling protein [KO:K08725]
110299690  Mc1r; melanocyte-stimulating hormone receptor [KO:K04199]
110308282  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
110308334  neuroendocrine secretory protein 55 [KO:K04632]
110305998  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
110307661  Adcy2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
110306494  Adcy3; adenylate cyclase type 3 isoform X2 [KO:K08043] [EC:4.6.1.1]
110309267  Adcy4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
110311373  Adcy5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
110310126  Adcy6; adenylate cyclase type 6 isoform X5 [KO:K08046] [EC:4.6.1.1]
110299719  Adcy7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
110310371  Adcy8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
110311555  Adcy9; adenylate cyclase type 9 isoform X2 [KO:K08049] [EC:4.6.1.1]
110290795  Prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X2 [KO:K04345] [EC:2.7.11.11]
110300173  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
110285614  Creb1; cyclic AMP-responsive element-binding protein 1 isoform X2 [KO:K05870]
110291408  Creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
110303337  Creb3l3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
110292754  Creb3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
110289497  Creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X2 [KO:K09048]
110296066  Creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
110310313  Ep300; LOW QUALITY PROTEIN: histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
110311224  Crebbp; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
110296033  Mitf; microphthalmia-associated transcription factor isoform X5 [KO:K09455]
110310964  Wnt1; proto-oncogene Wnt-1 [KO:K03209]
110296313  Wnt2; protein Wnt-2 [KO:K00182]
110291476  Wnt2b; protein Wnt-2b [KO:K00182]
110305853  Wnt3a; protein Wnt-3a [KO:K00312]
110304911  Wnt3; proto-oncogene Wnt-3 [KO:K00312]
110293218  Wnt4; protein Wnt-4 isoform X1 [KO:K00408]
110295760  Wnt5b; protein Wnt-5b [KO:K00444]
110309360  Wnt5a; protein Wnt-5a isoform X1 [KO:K00444]
110299810  Wnt6; protein Wnt-6 [KO:K00445]
110310689  Wnt7b; protein Wnt-7b isoform X1 [KO:K00572]
110296669  Wnt7a; protein Wnt-7a isoform X1 [KO:K00572]
110285759  Wnt8b; protein Wnt-8b [KO:K00714]
110285093  Wnt8a; protein Wnt-8a [KO:K00714]
110306039  Wnt9a; protein Wnt-9a [KO:K01064]
110305968  Wnt9b; protein Wnt-9b [KO:K01064]
110310912  Wnt10b; protein Wnt-10b isoform X1 [KO:K01357]
110300434  Wnt10a; protein Wnt-10a [KO:K01357]
110298907  Wnt11; protein Wnt-11 isoform X1 [KO:K01384]
110296883  Wnt16; protein Wnt-16 [KO:K01558]
110301431  Fzd7; frizzled-7 [KO:K02432]
110294363  Fzd1; frizzled-1 [KO:K02432]
110305336  Fzd2; frizzled-2 [KO:K02235]
110309352  Fzd3; frizzled-3 [KO:K02329]
110298417  Fzd4; frizzled-4 [KO:K02354]
110294401  Fzd5; frizzled-5 [KO:K02375]
110284745  Fzd8; frizzled-8 [KO:K02375]
110310580  Fzd6; frizzled-6 [KO:K02376]
110295350  Fzd9; frizzled-9 [KO:K02842]
110295197  Fzd10; frizzled-10 [KO:K02842]
110299754  Gnao1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
110285306  guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
110292264  Dvl1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
110304161  Dvl2; segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
110311604  Dvl3; segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
110311365  Gsk3b; glycogen synthase kinase-3 beta isoform X2 [KO:K03083] [EC:2.7.11.26]
110301052  Ctnnb1; catenin beta-1 [KO:K02105]
110304948  Tcf7; transcription factor 7 isoform X2 [KO:K02620]
110296038  Tcf7l1; transcription factor 7-like 1 isoform X2 [KO:K04490]
110285273  Tcf7l2; transcription factor 7-like 2 isoform X5 [KO:K04491]
110290892  Lef1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
110302981  Kitlg; kit ligand isoform X1 [KO:K05461]
110294693  Kit; mast/stem cell growth factor receptor Kit isoform X1 [KO:K05091] [EC:2.7.10.1]
110297313  Hras; GTPase HRas isoform X2 [KO:K02833]
110296194  Kras; GTPase KRas isoform X1 [KO:K07827]
110290873  Nras; GTPase NRas [KO:K07828]
110296919  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
110301502  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
110303196  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
110297836  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
110311382  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
110298406  Tyr; tyrosinase isoform X1 [KO:K00505] [EC:1.14.18.1]
110292114  Tyrp1; 5,6-dihydroxyindole-2-carboxylic acid oxidase [KO:K00506] [EC:1.14.18.-]
110308926  Dct; L-dopachrome tautomerase [KO:K01827] [EC:5.3.3.12]
110308576  Edn1; endothelin-1 [KO:K16366]
110309107  Ednrb; endothelin receptor type B [KO:K04198]
110290775  Gnai3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
110294623  Gnai1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
110301809  Gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
110285320  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
110290514  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
110286326  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
110308867  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X2 [KO:K05858] [EC:3.1.4.11]
110286675  calmodulin-alpha-like [KO:K02183]
110308577  Calml3; calmodulin-like protein 3 [KO:K02183]
110308601  calmodulin-4 [KO:K02183]
110286582  calmodulin [KO:K02183]
110306434  Calm1; calmodulin-1 [KO:K02183]
110302040  Calml4; calmodulin-like protein 4 isoform X2 [KO:K02183]
110297869  Calm3; calmodulin-3 [KO:K02183]
110294847  calmodulin-like [KO:K02183]
110312637  Calm2; calmodulin-2 [KO:K02183]
110309790  Camk2g; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X5 [KO:K04515] [EC:2.7.11.17]
110305925  Camk2b; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X5 [KO:K04515] [EC:2.7.11.17]
110290827  Camk2d; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X3 [KO:K04515] [EC:2.7.11.17]
110284502  Camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
110304357  Prkca; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
110297826  Prkcb; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
110297763  Prkcg; protein kinase C gamma type [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
  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
  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
  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
  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
  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
  Authors
Miller AJ, Mihm MC Jr.
  Title
Melanoma.
  Journal
N Engl J Med 355:51-65 (2006)
DOI:10.1056/NEJMra052166
Reference
  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
  Authors
Park HY, Gilchrest BA.
  Title
Signaling pathways mediating melanogenesis.
  Journal
Cell Mol Biol (Noisy-le-grand) 45:919-30 (1999)
Reference
  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
  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
  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
  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
mcal00350  Tyrosine metabolism
mcal04010  MAPK signaling pathway
mcal04310  Wnt signaling pathway
mcal05218  Melanoma
KO pathway
ko04916   
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