KEGG   PATHWAY: rtd04916
Entry
rtd04916                    Pathway                                
Name
Melanogenesis - Rissa tridactyla (black-legged kittiwake)
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
rtd04916  Melanogenesis
rtd04916

Organism
Rissa tridactyla (black-legged kittiwake) [GN:rtd]
Gene
128907077  POMC; pro-opiomelanocortin [KO:K05228]
128916517  ASIP; agouti-signaling protein isoform X1 [KO:K08725]
128916395  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
128905714  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
128905654  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
128907497  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
128912369  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
128901258  ADCY6; LOW QUALITY PROTEIN: adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
128908370  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
128906210  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
128913706  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
128913296  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
128913135  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
128900615  CREB3L3; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
128901026  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
128908730  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
128903007  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
128909881  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
128914368  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
128905360  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
128915501  MITF; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
128901276  WNT1; proto-oncogene Wnt-1 [KO:K03209]
128900435  WNT2B; protein Wnt-2b [KO:K00182]
128904097  WNT2; protein Wnt-2 [KO:K00182]
128919236  WNT3; proto-oncogene Wnt-3 [KO:K00312]
128905512  WNT3A; protein Wnt-3a [KO:K00312]
128918479  WNT4; protein Wnt-4 [KO:K00408]
128904407  protein Wnt-4-like [KO:K00408]
128918403  WNT5B; protein Wnt-5b isoform X1 [KO:K00444]
128915855  WNT5A; protein Wnt-5a [KO:K00444]
128913068  WNT6; protein Wnt-6 [KO:K00445]
128915611  WNT7A; protein Wnt-7a [KO:K00572]
128904299  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
128916196  WNT8A; protein Wnt-8a [KO:K00714]
128911135  WNT8B; protein Wnt-8b [KO:K00714]
128919237  WNT9B; protein Wnt-9b [KO:K01064]
128906141  WNT9A; protein Wnt-9a [KO:K01064]
128913062  WNT10A; LOW QUALITY PROTEIN: protein Wnt-10a [KO:K01357]
128915135  protein Wnt-11b-like isoform X1 [KO:K01384]
128904424  WNT11; protein Wnt-11 isoform X1 [KO:K01384]
128904539  WNT16; protein Wnt-16 [KO:K01558]
128913031  FZD7; frizzled-7 [KO:K02432]
128906196  FZD1; frizzled-1 [KO:K02432]
128919378  FZD2; frizzled-2 [KO:K02235]
128907037  FZD3; frizzled-3 isoform X1 [KO:K02329]
128918925  FZD4; frizzled-4 [KO:K02354]
128913133  FZD5; frizzled-5 [KO:K02375]
128906246  FZD8; frizzled-8 [KO:K02375]
128905894  FZD6; frizzled-6 [KO:K02376]
128917061  FZD10; frizzled-10 [KO:K02842]
128912316  FZD9; frizzled-9 [KO:K02842]
128908562  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
128901959  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
128902254  guanine nucleotide-binding protein G(q) subunit alpha-like isoform X1 [KO:K04634]
128918283  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
128911279  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
128917695  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
128905175  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
128915932  TCF7; transcription factor 7 isoform X1 [KO:K02620]
128919648  TCF7L1; LOW QUALITY PROTEIN: transcription factor 7-like 1 [KO:K04490]
128911762  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
128910491  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
128916171  KITLG; kit ligand isoform X1 [KO:K05461]
128909965  KIT; mast/stem cell growth factor receptor Kit isoform X1 [KO:K05091] [EC:2.7.10.1]
128908943  HRAS; GTPase HRas [KO:K02833]
128914000  KRAS; GTPase KRas isoform X1 [KO:K07827]
128900210  NRAS; GTPase NRas isoform X1 [KO:K07828]
128915881  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
128914576  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
128900734  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
128917291  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
128904187  TYR; tyrosinase [KO:K00505] [EC:1.14.18.1]
128902540  TYRP1; 5,6-dihydroxyindole-2-carboxylic acid oxidase [KO:K00506] [EC:1.14.18.-]
128915967  DCT; L-dopachrome tautomerase [KO:K01827] [EC:5.3.3.12]
128906341  EDN1; endothelin-1 [KO:K16366]
128902725  EDNRB; endothelin receptor type B [KO:K04198]
128914865  endothelin receptor type B-like [KO:K04198]
128900392  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 isoform X1 [KO:K04630]
128914128  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
128915754  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
128906836  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
128907839  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
128908469  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
128907192  CALM2; calmodulin-2 [KO:K02183]
128901738  CALM3; calmodulin-3 isoform X1 [KO:K02183]
128914539  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
128909523  CALM1; calmodulin-1 [KO:K02183]
128904890  calmodulin, striated muscle [KO:K02183]
128919596  CAMK2B; LOW QUALITY PROTEIN: calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
128910153  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
128916191  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
128911707  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
128917842  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
128913847  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
128903859  LOW QUALITY PROTEIN: protein kinase C gamma type-like [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
rtd00350  Tyrosine metabolism
rtd04010  MAPK signaling pathway
rtd04310  Wnt signaling pathway
KO pathway
ko04916   
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