KEGG   PATHWAY: ajm04916
Entry
ajm04916                    Pathway                                
Name
Melanogenesis - Artibeus jamaicensis (Jamaican fruit-eating bat)
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
ajm04916  Melanogenesis
ajm04916

Organism
Artibeus jamaicensis (Jamaican fruit-eating bat) [GN:ajm]
Gene
119050328  POMC; pro-opiomelanocortin [KO:K05228]
119047798  LOW QUALITY PROTEIN: agouti-signaling protein [KO:K08725]
119055313  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
119055349  neuroendocrine secretory protein 55-like [KO:K04632]
119057313  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
119049317  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
119050413  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
119037286  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
119039523  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
119042160  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
119046468  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
119064806  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
119056281  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
119062886  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
119049690  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
119064343  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
119061780  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
119048742  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
119063765  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
119064485  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
119065205  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
119060587  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
119056235  CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
119045197  MITF; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
119041907  WNT1; proto-oncogene Wnt-1 [KO:K03209]
119059356  WNT2; protein Wnt-2 isoform X1 [KO:K00182]
119054571  WNT2B; protein Wnt-2b isoform X1 [KO:K00182]
119045688  WNT3A; protein Wnt-3a [KO:K00312]
119062573  WNT3; proto-oncogene Wnt-3 [KO:K00312]
119042246  WNT4; protein Wnt-4 [KO:K00408]
119045185  WNT5B; protein Wnt-5b isoform X1 [KO:K00444]
119047017  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
119056890  WNT6; protein Wnt-6 [KO:K00445]
119060582  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
119045529  protein Wnt-7b-like [KO:K00572]
119065458  WNT7A; protein Wnt-7a [KO:K00572]
119059697  WNT8B; protein Wnt-8b [KO:K00714]
119051097  WNT8A; protein Wnt-8a [KO:K00714]
119045703  WNT9A; protein Wnt-9a isoform X1 [KO:K01064]
119062668  WNT9B; protein Wnt-9b [KO:K01064]
119042216  WNT10B; protein Wnt-10b [KO:K01357]
119056889  WNT10A; protein Wnt-10a [KO:K01357]
119038953  WNT11; protein Wnt-11 [KO:K01384]
119045059  WNT16; protein Wnt-16 [KO:K01558]
119042725  FZD1; frizzled-1 isoform X1 [KO:K02432]
119055279  FZD7; frizzled-7 [KO:K02432]
119061600  FZD2; frizzled-2 [KO:K02235]
119053028  FZD3; frizzled-3 [KO:K02329]
119047391  FZD4; frizzled-4 isoform X1 [KO:K02354]
119064203  FZD8; frizzled-8 [KO:K02375]
119064337  FZD5; frizzled-5 [KO:K02375]
119040403  FZD6; frizzled-6 isoform X1 [KO:K02376]
119060771  FZD10; frizzled-10 [KO:K02842]
119056364  FZD9; frizzled-9 [KO:K02842]
119046437  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
119052107  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
119037135  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
119056435  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
119050532  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
119059198  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
119051448  CTNNB1; catenin beta-1 [KO:K02105]
119037608  TCF7; transcription factor 7 isoform X1 [KO:K02620]
119059869  TCF7L1; transcription factor 7-like 1 [KO:K04490]
119040094  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
119061436  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
119036386  KITLG; kit ligand isoform X1 [KO:K05461]
119054285  KIT; mast/stem cell growth factor receptor Kit isoform X1 [KO:K05091] [EC:2.7.10.1]
119062206  HRAS; GTPase HRas isoform X1 [KO:K02833]
119048987  KRAS; GTPase KRas isoform X1 [KO:K07827]
119041711  NRAS; GTPase NRas [KO:K07828]
119044815  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
119057101  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
119063754  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
119040930  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
119059157  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
119043575  TYR; tyrosinase [KO:K00505] [EC:1.14.18.1]
119038709  TYRP1; 5,6-dihydroxyindole-2-carboxylic acid oxidase [KO:K00506] [EC:1.14.18.-]
119039673  DCT; L-dopachrome tautomerase [KO:K01827] [EC:5.3.3.12]
119054876  EDN1; endothelin-1 [KO:K16366]
119055905  EDNRB; endothelin receptor type B [KO:K04198]
119036589  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
119040343  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
119054511  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha isoform X1 [KO:K04630]
119045446  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
119061296  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
119057282  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
119035940  calmodulin-2/4 [KO:K02183]
119037894  CALM1; calmodulin-1 [KO:K02183]
119053333  calmodulin-2/4 [KO:K02183]
119060885  CALM2; calmodulin-2 [KO:K02183]
119056493  calmodulin-A-like [KO:K02183]
119056633  CALM3; calmodulin-3 [KO:K02183]
119057111  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
119057312  calmodulin-alpha-like [KO:K02183]
119057735  CALML3; calmodulin-like protein 3 [KO:K02183]
119050509  CALML6; calmodulin-like protein 6 [KO:K02183]
119037697  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
119038077  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
119052888  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
119061401  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
119036326  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
119043241  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
119036009  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
ajm00350  Tyrosine metabolism
ajm04010  MAPK signaling pathway
ajm04310  Wnt signaling pathway
ajm05218  Melanoma
KO pathway
ko04916   
LinkDB

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