KEGG   PATHWAY: ppad04916
Entry
ppad04916                   Pathway                                
Name
Melanogenesis - Panthera pardus (leopard)
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
ppad04916  Melanogenesis
ppad04916

Organism
Panthera pardus (leopard) [GN:ppad]
Gene
109262875  POMC; pro-opiomelanocortin [KO:K05228]
109272540  ASIP; agouti-signaling protein isoform X1 [KO:K08725]
109253465  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas-like isoform X1 [KO:K04632]
109253466  neuroendocrine secretory protein 55 [KO:K04632]
109267948  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
109267830  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
109267527  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
109254969  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
109266493  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
109249043  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
109270953  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
109273118  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
109278247  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
109246175  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
109253991  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
109265159  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
109270166  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
109256215  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
109245089  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
109255940  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
109269067  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
109278438  CREBBP; LOW QUALITY PROTEIN: CREB-binding protein [KO:K04498] [EC:2.3.1.48]
109265617  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
109254484  MITF; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
109249055  WNT1; proto-oncogene Wnt-1 [KO:K03209]
109248384  WNT2; protein Wnt-2 [KO:K00182]
109272063  WNT2B; protein Wnt-2b [KO:K00182]
109259603  protein Wnt-3a [KO:K00312]
109259748  WNT3; proto-oncogene Wnt-3 isoform X1 [KO:K00312]
109274277  WNT4; protein Wnt-4 isoform X1 [KO:K00408]
109279118  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
109276247  WNT5B; protein Wnt-5b [KO:K00444]
109265051  WNT6; protein Wnt-6 [KO:K00445]
109265719  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
109257500  WNT7A; protein Wnt-7a [KO:K00572]
109252095  WNT8A; protein Wnt-8a [KO:K00714]
109272682  WNT8B; protein Wnt-8b [KO:K00714]
109259601  WNT9A; protein Wnt-9a isoform X1 [KO:K01064]
109259736  WNT9B; protein Wnt-9b [KO:K01064]
109265050  WNT10A; protein Wnt-10a [KO:K01357]
109249054  WNT10B; protein Wnt-10b [KO:K01357]
109267221  WNT11; protein Wnt-11 [KO:K01384]
109268901  WNT16; protein Wnt-16 [KO:K01558]
109259199  FZD7; frizzled-7 [KO:K02432]
109263669  FZD1; frizzled-1 [KO:K02432]
109258237  FZD2; frizzled-2 [KO:K02235]
109262362  FZD3; frizzled-3 isoform X1 [KO:K02329]
109267311  FZD4; frizzled-4 isoform X1 [KO:K02354]
109276176  frizzled-8-like [KO:K02375]
109265155  FZD5; frizzled-5 [KO:K02375]
109276288  FZD8; frizzled-8 [KO:K02375]
109277964  FZD6; frizzled-6 [KO:K02376]
109257591  FZD10; frizzled-10 [KO:K02842]
109250592  FZD9; frizzled-9 [KO:K02842]
109270899  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
109275364  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
109273921  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
109275214  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
109245979  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
109266441  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
109248805  CTNNB1; catenin beta-1 [KO:K02105]
109250863  TCF7; transcription factor 7 isoform X1 [KO:K02620]
109263707  TCF7L1; transcription factor 7-like 1 isoform X1 [KO:K04490]
109272915  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
109247814  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
109265299  KITLG; kit ligand isoform X1 [KO:K05461]
109278960  KIT; mast/stem cell growth factor receptor Kit isoform X1 [KO:K05091] [EC:2.7.10.1]
109259759  GTPase HRas [KO:K02833]
109268745  KRAS; GTPase KRas isoform X1 [KO:K07827]
109272105  NRAS; GTPase NRas [KO:K07828]
109257492  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
109262816  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
109255967  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
109259699  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
109261343  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
109267329  TYR; tyrosinase isoform X1 [KO:K00505] [EC:1.14.18.1]
109247101  TYRP1; 5,6-dihydroxyindole-2-carboxylic acid oxidase [KO:K00506] [EC:1.14.18.-]
109264168  DCT; L-dopachrome tautomerase [KO:K01827] [EC:5.3.3.12]
109249630  EDN1; endothelin-1 isoform X1 [KO:K16366]
109264200  EDNRB; endothelin B receptor [KO:K04198]
109247840  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
109268145  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
109272000  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
109246661  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
109274721  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
109274722  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
109263166  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
109273951  calmodulin-like protein 6 isoform X1 [KO:K02183]
109246761  CALM2; calmodulin [KO:K02183]
109253192  CALM3; calmodulin isoform X1 [KO:K02183]
109273783  calmodulin-like protein 3 [KO:K02183]
109273784  calmodulin-like [KO:K02183]
109273854  calmodulin-like protein 6 [KO:K02183]
109274449  CALM1; calmodulin [KO:K02183]
109262791  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
109257442  calmodulin-alpha-like [KO:K02183]
109262226  calmodulin-like [KO:K02183]
109264424  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
109275954  calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
109248360  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
109267916  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
109277056  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
109255537  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
109259277  PRKCG; protein kinase C gamma type isoform X1 [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
ppad00350  Tyrosine metabolism
ppad04010  MAPK signaling pathway
ppad04310  Wnt signaling pathway
ppad05218  Melanoma
KO pathway
ko04916   
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