KEGG   PATHWAY: gga04916
Entry
gga04916                    Pathway                                
Name
Melanogenesis - Gallus gallus (chicken)
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
gga04916  Melanogenesis
gga04916

Organism
Gallus gallus (chicken) [GN:gga]
Gene
422011  POMC; pro-opiomelanocortin precursor [KO:K05228]
419147  ASIP; agouti-signaling protein precursor [KO:K08725]
427562  MC1R; melanocyte-stimulating hormone receptor [KO:K04199]
419313  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
420788  ADCY1; adenylate cyclase type 1 isoform X2 [KO:K08041] [EC:4.6.1.1]
420935  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
422013  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
395340  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
107050028  adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
415732  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
420328  ADCY8; adenylate cyclase type 8 isoform X2 [KO:K08048] [EC:4.6.1.1]
395339  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
424542  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X7 [KO:K04345] [EC:2.7.11.11]
395099  CREB1; cyclic AMP-responsive element-binding protein 1 [KO:K05870]
427417  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
418123  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X2 [KO:K09048]
428333  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
100859610  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X2 [KO:K09048]
416667  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
418000  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
395886  MITF; microphthalmia-associated transcription factor [KO:K09455]
396160  WNT1; protein Wnt-1 [KO:K03209]
374243  WNT2B; protein Wnt-2b precursor [KO:K00182]
417769  WNT2; protein Wnt-2 [KO:K00182]
395396  WNT3A; protein Wnt-3a isoform 1 precursor [KO:K00312]
374142  WNT3; proto-oncogene Wnt-3 [KO:K00312]
395561  WNT4; protein Wnt-4 precursor [KO:K00408]
395703  WNT5A; protein Wnt-5a [KO:K00444]
418154  WNT5B; protein Wnt-5b precursor [KO:K00444]
395235  WNT6; protein Wnt-6 [KO:K00445]
374168  WNT7A; protein Wnt-7a [KO:K00572]
427937  WNT7B; protein Wnt-7b isoform 1 precursor [KO:K00572]
428953  WNT8B; protein Wnt-8b isoform X1 [KO:K00714]
396543  WNT8A; protein Wnt-8c precursor [KO:K00714]
395829  WNT9A; protein Wnt-9a precursor [KO:K01064]
771092  WNT9B; protein Wnt-9b [KO:K01064]
429040  WNT10A; protein Wnt-10a precursor [KO:K01357]
395562  WNT11; protein Wnt-11 precursor [KO:K01384]
100170842  WNT11B; protein Wnt-11 precursor [KO:K01384]
427856  WNT16; protein Wnt-16 [KO:K01558]
374062  FZD1; frizzled-1 precursor [KO:K02432]
374060  FZD7; frizzled-7 precursor [KO:K02432]
374061  FZD2; frizzled-2 precursor [KO:K02235]
395572  FZD3; frizzled-3 precursor [KO:K02329]
373887  FZD4; frizzled-4 precursor [KO:K02354]
395571  FZD5; frizzled-5 precursor [KO:K02375]
374059  FZD8; LOW QUALITY PROTEIN: frizzled-8 [KO:K02375]
378788  FZD6; frizzled-6 precursor [KO:K02376]
373885  FZD10; frizzled-10 precursor [KO:K02842]
373886  FZD9; frizzled-9 precursor [KO:K02842]
415698  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
427262  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
424949  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X6 [KO:K02353]
419416  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
418335  GSK3B; glycogen synthase kinase-3 beta isoform X2 [KO:K03083] [EC:2.7.11.26]
395964  CTNNB1; catenin beta-1 [KO:K02105]
395229  TCF7; transcription factor 7 [KO:K02620]
395230  TCF7L1; transcription factor 7-like 1 isoform X1 [KO:K04490]
395508  TCF7L2; transcription factor 7-like 2 [KO:K04491]
395865  LEF1; lymphoid enhancer-binding factor 1 [KO:K04492]
396028  KITLG; kit ligand isoform 1 precursor [KO:K05461]
378783  KIT; mast/stem cell growth factor receptor Kit precursor [KO:K05091] [EC:2.7.10.1]
396229  HRAS; GTPase HRas precursor [KO:K02833]
418207  KRAS; GTPase KRas [KO:K07827]
419885  NRAS; GTPase NRas precursor [KO:K07828]
396245  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
415549  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
396349  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
373953  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
373971  TYR; tyrosinase precursor [KO:K00505] [EC:1.14.18.1]
395913  TYRP1; 5,6-dihydroxyindole-2-carboxylic acid oxidase precursor [KO:K00506] [EC:1.14.18.-]
395775  DCT; L-dopachrome tautomerase precursor [KO:K01827] [EC:5.3.3.12]
420854  EDN1; endothelin-1 [KO:K16366]
373909  EDNRB2; endothelin receptor B subtype 2 precursor [KO:K04198]
408082  EDNRB; endothelin receptor type B precursor [KO:K04198]
374097  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
396367  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
396368  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
423014  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X2 [KO:K05858] [EC:3.1.4.11]
416730  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
427687  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
396523  CALM1; neo-calmodulin [KO:K02183]
416692  CALML3; calmodulin, striated muscle [KO:K02183]
395855  CALM2; calmodulin [KO:K02183]
427515  CALML4; calmodulin-like protein 4 [KO:K02183]
374174  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
374175  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
423737  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
422688  CAMK2D; calcium/calmodulin-dependent protein kinase type II delta chain [KO:K04515] [EC:2.7.11.17]
417430  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
416567  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [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
gga00350  Tyrosine metabolism
gga04010  MAPK signaling pathway
gga04310  Wnt signaling pathway
KO pathway
ko04916   
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