KEGG   PATHWAY: dle04916
Entry
dle04916                    Pathway                                
Name
Melanogenesis - Delphinapterus leucas (beluga whale)
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
dle04916  Melanogenesis
dle04916

Organism
Delphinapterus leucas (beluga whale) [GN:dle]
Gene
111163022  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
111163319  WNT4; protein Wnt-4 isoform X1 [KO:K00408]
111163585  KITLG; kit ligand isoform X1 [KO:K05461]
111164225  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
111164400  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
111164599  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
111164991  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
111165310  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
111165393  TCF7L1; transcription factor 7-like 1 isoform X1 [KO:K04490]
111165617  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
111165653  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
111165994  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
111166195  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
111166674  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
111167181  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
111168040  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
111168811  WNT7A; protein Wnt-7a [KO:K00572]
111168973  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
111169279  WNT9A; protein Wnt-9a [KO:K01064]
111169289  WNT3A; protein Wnt-3a [KO:K00312]
111169438  CTNNB1; catenin beta-1 [KO:K02105]
111169672  KIT; mast/stem cell growth factor receptor Kit isoform X1 [KO:K05091] [EC:2.7.10.1]
111170127  [KO:K02183]
111170218  FZD2; frizzled-2 [KO:K02235]
111170340  HRAS; GTPase HRas isoform X1 [KO:K02833]
111171490  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
111171650  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
111171737  FZD7; frizzled-7 [KO:K02432]
111171769  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
111171775  FZD5; frizzled-5 [KO:K02375]
111172090  WNT6; protein Wnt-6 [KO:K00445]
111172091  WNT10A; protein Wnt-10a [KO:K01357]
111172300  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
111172662  WNT8B; protein Wnt-8b [KO:K00714]
111173388  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
111174035  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
111174054  WNT10B; protein Wnt-10b [KO:K01357]
111174055  WNT1; proto-oncogene Wnt-1 [KO:K03209]
111174194  MITF; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
111174269  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
111174368  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
111174571  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
111174675  TYRP1; 5,6-dihydroxyindole-2-carboxylic acid oxidase [KO:K00506] [EC:1.14.18.-]
111174766  POMC; pro-opiomelanocortin [KO:K05228]
111174794  CALM2; calmodulin-2 [KO:K02183]
111175000  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
111176162  CALM1; calmodulin-1 [KO:K02183]
111176330  DCT; L-dopachrome tautomerase [KO:K01827] [EC:5.3.3.12]
111176474  EDNRB; endothelin receptor type B [KO:K04198]
111176602  WNT5B; protein Wnt-5b [KO:K00444]
111176851  KRAS; GTPase KRas [KO:K07827]
111177745  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
111177758  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
111177938  FZD8; frizzled-8 [KO:K02375]
111177962  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
111178380  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
111178556  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
111179093  WNT16; protein Wnt-16 [KO:K01558]
111179238  WNT2; protein Wnt-2 [KO:K00182]
111179996  NRAS; GTPase NRas [KO:K07828]
111180026  WNT2B; protein Wnt-2b isoform X1 [KO:K00182]
111180070  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
111180361  FZD6; frizzled-6 [KO:K02376]
111180711  CALM3; calmodulin-3 [KO:K02183]
111180740  FZD1; frizzled-1 [KO:K02432]
111180981  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
111181269  EDN1; endothelin-1 [KO:K16366]
111181753  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
111182181  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
111182232  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
111182319  FZD9; frizzled-9 [KO:K02842]
111182442  TCF7; transcription factor 7 isoform X1 [KO:K02620]
111182565  WNT8A; protein Wnt-8a [KO:K00714]
111182576  WNT3; proto-oncogene Wnt-3 [KO:K00312]
111182917  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
111182925  WNT9B; protein Wnt-9b [KO:K01064]
111183091  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
111183530  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
111183812  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
111183987  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
111184266  ASIP; agouti-signaling protein isoform X1 [KO:K08725]
111184516  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
111184534  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
111184814  WNT11; protein Wnt-11 [KO:K01384]
111184818  TYR; tyrosinase [KO:K00505] [EC:1.14.18.1]
111184951  FZD4; frizzled-4 [KO:K02354]
111185248  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
111185250  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
111185390  FZD3; frizzled-3 [KO:K02329]
111185664  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X4 [KO:K02353]
111186068  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
111186418  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
111186470  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
111186741  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
111186746  [KO:K04632]
111186950  FZD10; frizzled-10 [KO:K02842]
111187117  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
111187200  CALML6; calmodulin-like protein 6 [KO:K02183]
111188007  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
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
dle00350  Tyrosine metabolism
dle04010  MAPK signaling pathway
dle04310  Wnt signaling pathway
dle05218  Melanoma
KO pathway
ko04916   

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