KEGG   PATHWAY: leri04916
Entry
leri04916                   Pathway                                
Name
Melanogenesis - Leucoraja erinacea (little skate)
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
leri04916  Melanogenesis
leri04916

Organism
Leucoraja erinacea (little skate) [GN:leri]
Gene
129699832  pomca; proopiomelanocortin a [KO:K05228]
129707336  asip1; agouti signaling protein 1 [KO:K08725]
129707193  gnas; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
129710284  adenylate cyclase type 1-like [KO:K08041] [EC:4.6.1.1]
129705029  adcy7; adenylate cyclase type 7 isoform X1 [KO:K08042] [EC:4.6.1.1]
129711549  LOW QUALITY PROTEIN: adenylate cyclase type 2-like [KO:K08042] [EC:4.6.1.1]
129699833  LOW QUALITY PROTEIN: adenylate cyclase type 3-like [KO:K08043] [EC:4.6.1.1]
129699122  adcy5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
129696342  adcy8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
129699829  adenylate cyclase type 8-like [KO:K08048] [EC:4.6.1.1]
129706900  adcy9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
129700701  LOW QUALITY PROTEIN: cAMP-dependent protein kinase catalytic subunit beta-like [KO:K04345] [EC:2.7.11.11]
129714364  LOW QUALITY PROTEIN: cAMP-dependent protein kinase catalytic subunit alpha-like [KO:K04345] [EC:2.7.11.11]
129698910  cyclic AMP-responsive element-binding protein 1-like isoform X1 [KO:K05870]
129695682  creb3l3l; cAMP responsive element binding protein 3-like 3 like [KO:K09048]
129705869  creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
129706242  creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
129711244  cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
129713867  ep300b; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
129706899  CREB-binding protein-like isoform X1 [KO:K04498] [EC:2.3.1.48]
129704516  microphthalmia-associated transcription factor-like isoform X1 [KO:K09455]
129714702  wnt1; LOW QUALITY PROTEIN: protein Wnt-1 [KO:K03209]
129706507  wnt2; protein Wnt-2 [KO:K00182]
129708591  protein Wnt-2b-A [KO:K00182]
129710210  wnt3; proto-oncogene Wnt-3 [KO:K00312]
129715050  wnt3a; protein Wnt-3a [KO:K00312]
129711438  wnt4; protein Wnt-4a [KO:K00408]
129706131  wnt5b; protein Wnt-5b isoform X1 [KO:K00444]
129704446  wnt5a; protein Wnt-5a isoform X1 [KO:K00444]
129714681  protein Wnt-6-like [KO:K00445]
129716130  LOW QUALITY PROTEIN: protein Wnt-6-like [KO:K00445]
129706146  protein Wnt-7b isoform X1 [KO:K00572]
129704822  wnt7aa; wingless-type MMTV integration site family, member 7Aa isoform X1 [KO:K00572]
129701745  protein Wnt-8-like [KO:K00714]
129712843  wnt8b; protein Wnt-8b [KO:K00714]
129710212  protein Wnt-9b-like isoform X1 [KO:K01064]
129715048  protein Wnt-9a-like [KO:K01064]
129714727  wnt10b; protein Wnt-10b [KO:K01357]
129716129  protein Wnt-10a-like [KO:K01357]
129702375  protein Wnt-11b-like [KO:K01384]
129698400  protein Wnt-11-like [KO:K01384]
129706497  wnt16; protein Wnt-16 [KO:K01558]
129709497  frizzled-1-like [KO:K02432]
129710386  fzd2; frizzled-2 [KO:K02235]
129697012  frizzled-3 isoform X1 [KO:K02329]
129698242  fzd4; frizzled-4 [KO:K02354]
129698914  fzd5; frizzled-5 [KO:K02375]
129715412  fzd8a; frizzled-8a [KO:K02375]
129696752  frizzled-6-like [KO:K02376]
129709371  fzd10; frizzled-10 [KO:K02842]
129710747  fzd9a; frizzled-9 [KO:K02842]
129705161  guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
129695757  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
129711338  guanine nucleotide-binding protein G(q) subunit alpha-like [KO:K04634]
129711340  guanine nucleotide-binding protein subunit alpha-11-like [KO:K04634]
129703400  segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
129711570  segment polarity protein dishevelled homolog DVL-1-like isoform X1 [KO:K02353]
129694018  dvl2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
129702546  gsk3ba; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
129707849  ctnnb1; catenin beta-1 isoform X1 [KO:K02105]
129701802  tcf7; transcription factor 7 isoform X1 [KO:K02620]
129713291  transcription factor 7-like 2 [KO:K04490]
129704026  tcf7l2; transcription factor 7-like 2 isoform X1 [KO:K04491]
129701019  lef1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
129706351  kitlga; kit ligand a isoform X1 [KO:K05461]
129697451  kita; mast/stem cell growth factor receptor kita isoform X1 [KO:K05091] [EC:2.7.10.1]
129705671  kras; GTPase KRas [KO:K02833]
129694991  GTPase HRas-like [KO:K07827]
129707662  GTPase KRas isoform X1 [KO:K07827]
129708834  nras; GTPase NRas [KO:K07828]
129704842  raf1b; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
129712705  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
129711246  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
129709053  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
129698248  tyr; tyrosinase [KO:K00505] [EC:1.14.18.1]
129695549  5,6-dihydroxyindole-2-carboxylic acid oxidase-like [KO:K00506] [EC:1.14.18.-]
129698003  dct; L-dopachrome tautomerase [KO:K01827] [EC:5.3.3.12]
129707894  edn1; endothelin-1 [KO:K16366]
129702179  endothelin receptor type B-like [KO:K04198]
129697975  endothelin receptor type B-like [KO:K04198]
129708880  guanine nucleotide-binding protein G(i) subunit alpha-3-like [KO:K04630]
129707792  gnai1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
129693758  guanine nucleotide-binding protein G(i) subunit alpha-1-like [KO:K04630]
129704748  guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630]
129699284  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
129699288  LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
129700502  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2-like [KO:K05858] [EC:3.1.4.11]
129715851  LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1-like [KO:K05858] [EC:3.1.4.11]
129699639  calm2b; calmodulin 2b, (phosphorylase kinase, delta) [KO:K02183]
129700047  calm1a; calmodulin-1a [KO:K02183]
129711692  calglandulin-like [KO:K02183]
129712743  calmodulin-like protein 4 [KO:K02183]
129701572  calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
129713199  calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
129700367  calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
129712893  camk2g2; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
129708162  protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
129706860  protein kinase C beta type isoform X1 [KO:K19662] [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
leri00350  Tyrosine metabolism
leri04010  MAPK signaling pathway
leri04310  Wnt signaling pathway
KO pathway
ko04916   
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