KEGG   PATHWAY: sbq04916
Entry
sbq04916                    Pathway                                
Name
Melanogenesis - Saimiri boliviensis boliviensis (Bolivian squirrel monkey)
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
sbq04916  Melanogenesis
sbq04916

Organism
Saimiri boliviensis boliviensis (Bolivian squirrel monkey) [GN:sbq]
Gene
101041563  POMC; pro-opiomelanocortin [KO:K05228]
101043452  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
104652116  neuroendocrine secretory protein 55 [KO:K04632]
101027981  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
101043334  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
101040601  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
101044688  ADCY4; adenylate cyclase type 4 isoform X2 [KO:K08044] [EC:4.6.1.1]
101049747  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
101037803  ADCY6; adenylate cyclase type 6 isoform X2 [KO:K08046] [EC:4.6.1.1]
101032672  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
101034552  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
101052034  ADCY9; adenylate cyclase type 9 isoform X2 [KO:K08049] [EC:4.6.1.1]
101034152  cAMP-dependent protein kinase catalytic subunit gamma-like [KO:K04345] [EC:2.7.11.11]
101036705  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
101043989  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma isoform X1 [KO:K04345] [EC:2.7.11.11]
101047300  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
101034085  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
101042795  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
101044974  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
101036473  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
101052885  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
101041199  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X4 [KO:K09048]
101033803  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
101050224  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
101044788  MITF; microphthalmia-associated transcription factor isoform X2 [KO:K09455]
101044133  WNT1; proto-oncogene Wnt-1 [KO:K03209]
101037307  WNT2; protein Wnt-2 [KO:K00182]
101051098  WNT2B; protein Wnt-2b isoform X1 [KO:K00182]
101035500  WNT3A; protein Wnt-3a [KO:K00312]
101048838  WNT3; proto-oncogene Wnt-3 isoform X1 [KO:K00312]
101050255  WNT4; protein Wnt-4 [KO:K00408]
101038250  WNT5B; protein Wnt-5b isoform X1 [KO:K00444]
101040063  WNT5A; protein Wnt-5a isoform X2 [KO:K00444]
101028364  WNT6; protein Wnt-6 [KO:K00445]
101027644  WNT7A; protein Wnt-7a [KO:K00572]
101041057  WNT8B; protein Wnt-8b [KO:K00714]
101037830  WNT8A; LOW QUALITY PROTEIN: protein Wnt-8a [KO:K00714]
104650180  WNT9B; protein Wnt-9b [KO:K01064]
101029432  WNT10A; protein Wnt-10a [KO:K01357]
101043819  WNT10B; protein Wnt-10b [KO:K01357]
101050295  WNT11; protein Wnt-11 [KO:K01384]
101032778  WNT16; protein Wnt-16 isoform X1 [KO:K01558]
101030044  FZD1; frizzled-1 [KO:K02432]
101049451  FZD7; frizzled-7 [KO:K02432]
101046720  FZD2; frizzled-2 [KO:K02235]
101037304  FZD3; frizzled-3 [KO:K02329]
101054300  FZD4; frizzled-4 [KO:K02354]
101036058  FZD5; frizzled-5 [KO:K02375]
101047742  FZD6; frizzled-6 [KO:K02376]
101030134  FZD9; frizzled-9 [KO:K02842]
101032028  FZD10; frizzled-10 [KO:K02842]
101049046  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
101051855  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
101035529  DVL1; segment polarity protein dishevelled homolog DVL-1 [KO:K02353]
101028835  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
101044711  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
101051107  GSK3B; glycogen synthase kinase-3 beta isoform X2 [KO:K03083] [EC:2.7.11.26]
101043327  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
101029076  TCF7; LOW QUALITY PROTEIN: transcription factor 7 [KO:K02620]
101033762  TCF7L1; transcription factor 7-like 1 [KO:K04490]
101037011  TCF7L2; transcription factor 7-like 2 [KO:K04491]
101047688  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
101047247  KITLG; kit ligand isoform X1 [KO:K05461]
101037282  KIT; mast/stem cell growth factor receptor Kit isoform X4 [KO:K05091] [EC:2.7.10.1]
101047663  HRAS; GTPase HRas isoform X2 [KO:K02833]
101047035  KRAS; GTPase KRas isoform X1 [KO:K07827]
101036877  NRAS; GTPase NRas [KO:K07828]
101054052  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
101040361  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
101036151  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101038546  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101043202  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101043674  TYR; tyrosinase [KO:K00505] [EC:1.14.18.1]
101050337  TYRP1; 5,6-dihydroxyindole-2-carboxylic acid oxidase [KO:K00506] [EC:1.14.18.-]
101052988  EDN1; endothelin-1 isoform X2 [KO:K16366]
101052365  EDNRB; endothelin B receptor [KO:K04198]
101042629  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
101041681  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630]
101032105  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
101046851  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X3 [KO:K05858] [EC:3.1.4.11]
101047168  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X2 [KO:K05858] [EC:3.1.4.11]
101052271  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
101029401  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
101036413  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
101031785  calmodulin-alpha-like [KO:K02183]
101041174  CALML6; calmodulin-like protein 6 isoform X2 [KO:K02183]
101029957  CALM3; calmodulin [KO:K02183]
101047982  CALM2; calmodulin [KO:K02183]
101039332  CALML3; calmodulin-like protein 3 [KO:K02183]
101039863  CALML5; calmodulin-like protein 5 [KO:K02183]
101049022  CALM1; LOW QUALITY PROTEIN: calmodulin [KO:K02183]
101031635  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
101041452  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
101052251  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
101041781  LOW QUALITY PROTEIN: calcium/calmodulin-dependent protein kinase type II delta chain-like [KO:K04515] [EC:2.7.11.17]
101038342  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X10 [KO:K04515] [EC:2.7.11.17]
101046010  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
101039384  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
101032613  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
PMID:15383650
  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
PMID:10841026
  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
PMID:15016298
  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
PMID:11023702
  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
PMID:12894244
  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
PMID:16822996
  Authors
Miller AJ, Mihm MC Jr.
  Title
Melanoma.
  Journal
N Engl J Med 355:51-65 (2006)
DOI:10.1056/NEJMra052166
Reference
PMID:12753399
  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
PMID:10643996
  Authors
Park HY, Gilchrest BA.
  Title
Signaling pathways mediating melanogenesis.
  Journal
Cell Mol Biol (Noisy-le-grand) 45:919-30 (1999)
Reference
PMID:10347209
  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
PMID:11602344
  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
PMID:11041354
  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
PMID:16246839
  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
sbq00350  Tyrosine metabolism
sbq04010  MAPK signaling pathway
sbq04310  Wnt signaling pathway
sbq05218  Melanoma
KO pathway
ko04916   
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