KEGG   PATHWAY: elk04916
Entry
elk04916                    Pathway                                
Name
Melanogenesis - Enhydra lutris kenyoni (northern sea otter)
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
elk04916  Melanogenesis
elk04916

Organism
Enhydra lutris kenyoni (northern sea otter) [GN:elk]
Gene
111154189  pro-opiomelanocortin [KO:K05228]
111141926  agouti-signaling protein [KO:K08725]
111141614  LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas [KO:K04632]
111141312  neuroendocrine secretory protein 55 [KO:K04632]
111157054  adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
111153427  adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
111154044  adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
111162403  adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
111155044  adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
111157825  adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
111157326  adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
111146667  adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
111156133  adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
111162516  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
111143399  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
111147575  cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
111151973  cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
111146280  cyclic AMP-responsive element-binding protein 3 [KO:K09048]
111150050  cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
111138943  cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
111161856  cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
111157665  histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
111156131  LOW QUALITY PROTEIN: CREB-binding protein [KO:K04498] [EC:2.3.1.48]
111143979  microphthalmia-associated transcription factor isoform X1 [KO:K09455]
111158015  proto-oncogene Wnt-1 [KO:K03209]
111143458  protein Wnt-2b [KO:K00182]
111152038  protein Wnt-2 [KO:K00182]
111139433  protein Wnt-3a [KO:K00312]
111158156  proto-oncogene Wnt-3 [KO:K00312]
111154909  protein Wnt-4 [KO:K00408]
111159795  protein Wnt-5b [KO:K00444]
111144172  protein Wnt-5a isoform X1 [KO:K00444]
111145739  LOW QUALITY PROTEIN: protein Wnt-6 [KO:K00445]
111157688  protein Wnt-7b isoform X1 [KO:K00572]
111159004  protein Wnt-7a [KO:K00572]
111141267  protein Wnt-8a [KO:K00714]
111145241  protein Wnt-8b [KO:K00714]
111139428  protein Wnt-9a [KO:K01064]
111158202  LOW QUALITY PROTEIN: protein Wnt-9b [KO:K01064]
111157990  protein Wnt-10b [KO:K01357]
111144711  protein Wnt-10a [KO:K01357]
111159478  protein Wnt-11 [KO:K01384]
111152110  protein Wnt-16 [KO:K01558]
111141425  frizzled-7 [KO:K02432]
111147325  frizzled-1 [KO:K02432]
111158141  frizzled-2 [KO:K02235]
111156239  frizzled-3 [KO:K02329]
111154467  frizzled-4 [KO:K02354]
111155536  LOW QUALITY PROTEIN: frizzled-8 [KO:K02375]
111143924  frizzled-5 [KO:K02375]
111146642  frizzled-6 [KO:K02376]
111156537  frizzled-10 [KO:K02842]
111146438  frizzled-9 [KO:K02842]
111157367  guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
111153498  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
111154625  segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
111161117  LOW QUALITY PROTEIN: segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
111148907  LOW QUALITY PROTEIN: segment polarity protein dishevelled homolog DVL-3-like [KO:K02353]
111149303  segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
111149921  glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
111159001  catenin beta-1 [KO:K02105]
111141244  transcription factor 7 isoform X1 [KO:K02620]
111148131  transcription factor 7-like 1 isoform X1 [KO:K04490]
111145217  transcription factor 7-like 2 isoform X1 [KO:K04491]
111154120  lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
111142191  kit ligand [KO:K05461]
111148912  mast/stem cell growth factor receptor Kit isoform X1 [KO:K05091] [EC:2.7.10.1]
111140316  GTPase HRas isoform X1 [KO:K02833]
111159984  GTPase KRas isoform X1 [KO:K07827]
111143238  GTPase NRas [KO:K07828]
111144322  RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
111153158  dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
111161815  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
111162236  LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
111142759  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
111154441  tyrosinase [KO:K00505] [EC:1.14.18.1]
111156610  5,6-dihydroxyindole-2-carboxylic acid oxidase [KO:K00506] [EC:1.14.18.-]
111147121  L-dopachrome tautomerase [KO:K01827] [EC:5.3.3.12]
111156738  endothelin-1 [KO:K16366]
111146994  endothelin receptor type B [KO:K04198]
111155312  guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
111143783  guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
111143343  guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
111141432  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
111162302  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
111141620  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
111150005  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
111158594  calmodulin-like [KO:K02183]
111158606  calmodulin-like protein 3 [KO:K02183]
111154855  calmodulin-like protein 6 [KO:K02183]
111160633  calmodulin-3 [KO:K02183]
111155835  calmodulin-2 [KO:K02183]
111148494  calmodulin-1 isoform X1 [KO:K02183]
111153268  calmodulin-like protein 4 isoform X1 [KO:K02183]
111140840  calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
111145432  calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
111153485  calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
111156985  calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
111158087  protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
111162208  protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
111139613  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
elk00350  Tyrosine metabolism
elk04010  MAPK signaling pathway
elk04310  Wnt signaling pathway
elk05218  Melanoma
KO pathway
ko04916   
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