KEGG   PATHWAY: psex04916
Entry
psex04916                   Pathway                                
Name
Melanogenesis - Polypterus senegalus (gray bichir)
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
psex04916  Melanogenesis
psex04916

Organism
Polypterus senegalus (gray bichir) [GN:psex]
Gene
120526116  pomca; proopiomelanocortin a isoform X1 [KO:K05228]
120535510  mc1r; melanocyte-stimulating hormone receptor [KO:K04199]
120514201  gnas; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
120529518  adenylate cyclase type 1-like [KO:K08041] [EC:4.6.1.1]
120515751  adenylate cyclase type 2-like [KO:K08042] [EC:4.6.1.1]
120526110  adcy3a; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
120524043  adenylate cyclase type 2-like [KO:K08044] [EC:4.6.1.1]
120530718  adcy5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
120524822  adcy6a; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
120535204  adcy7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
120529809  adcy8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
120543008  adcy9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
120514851  prkacba; protein kinase, cAMP-dependent, catalytic, beta a isoform X1 [KO:K04345] [EC:2.7.11.11]
120541109  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
120530753  creb1b; cyclic AMP-responsive element-binding protein 1b [KO:K05870]
120537773  cyclic AMP-responsive element-binding protein 3-like protein 3-A isoform X1 [KO:K09048]
120530363  creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
120539312  creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
120532997  creb3l3l; cAMP responsive element binding protein 3-like 3 like isoform X1 [KO:K09048]
120528524  creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
120541898  CREB-binding protein-like isoform X1 [KO:K04498] [EC:2.3.1.48]
120536925  ep300b; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
120540282  microphthalmia-associated transcription factor-like isoform X1 [KO:K09455]
120525165  wnt1; protein Wnt-1 [KO:K03209]
120526346  wnt2bb; wingless-type MMTV integration site family, member 2Bb [KO:K00182]
120534112  wnt2; protein Wnt-2 isoform X1 [KO:K00182]
120518210  wnt3; proto-oncogene Wnt-3 [KO:K00312]
120529458  wnt3a; protein Wnt-3a isoform X1 [KO:K00312]
120530956  wnt4; protein Wnt-4a isoform X1 [KO:K00408]
120535670  protein Wnt-4-like [KO:K00408]
120533684  wnt5b; protein Wnt-5b isoform X1 [KO:K00444]
120531727  wnt6b; protein Wnt-6 isoform X1 [KO:K00445]
120539385  protein Wnt-7b isoform X1 [KO:K00572]
120540345  wnt7aa; wingless-type MMTV integration site family, member 7Aa isoform X1 [KO:K00572]
120541195  wnt8b; protein Wnt-8b [KO:K00714]
120542717  protein Wnt-8a-like [KO:K00714]
120542769  protein Wnt-8-like [KO:K00714]
120517497  wnt9b; protein Wnt-9b [KO:K01064]
120529460  wnt9a; protein Wnt-9a [KO:K01064]
120531728  wnt10a; protein Wnt-10a [KO:K01357]
120525166  wnt10b; protein Wnt-10b [KO:K01357]
120523349  wnt11; protein Wnt-11 [KO:K01384]
120536256  wnt11f2; protein Wnt-11 [KO:K01384]
120534006  wnt16; protein Wnt-16 [KO:K01558]
120531940  fzd7b; frizzled-7b [KO:K02432]
120515446  frizzled-1-like [KO:K02432]
120517695  frizzled-2 [KO:K02235]
120526108  frizzled-3 [KO:K02329]
120523155  fzd4; frizzled-4 [KO:K02354]
120530750  fzd5; frizzled-5 [KO:K02375]
120529612  fzd8a; frizzled-8a [KO:K02375]
120516148  frizzled-6-like [KO:K02376]
120531448  fzd9a; frizzled-9 [KO:K02842]
120540908  fzd10; frizzled-10 [KO:K02842]
120535274  gnao1a; guanine nucleotide binding protein (G protein), alpha activating activity polypeptide O, a isoform X1 [KO:K04534]
120527303  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
120531107  dvl1a; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
120540173  segment polarity protein dishevelled homolog DVL-3-like [KO:K02353]
120524993  dvl2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
120536531  LOW QUALITY PROTEIN: segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
120522916  gsk3ba; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
120516099  ctnnb1; catenin beta-1 isoform X1 [KO:K02105]
120542075  tcf7; transcription factor 7 isoform X1 [KO:K02620]
120538925  tcf7l1a; transcription factor 7-like 1-A isoform X1 [KO:K04490]
120543224  tcf7l2; transcription factor 7-like 2 isoform X1 [KO:K04491]
120532281  lef1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
120527609  kita; mast/stem cell growth factor receptor kita [KO:K05091] [EC:2.7.10.1]
120523258  GTPase HRas [KO:K02833]
120534191  GTPase KRas isoform X1 [KO:K07827]
120542190  GTPase HRas-like [KO:K07827]
120526283  nras; GTPase NRas [KO:K07828]
120540276  raf1b; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
120541670  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
120537759  map2k2a; dual specificity mitogen-activated protein kinase kinase 2a [KO:K04369] [EC:2.7.12.2]
120540631  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
120536571  mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
120519559  tyrosinase-like [KO:K00505] [EC:1.14.18.1]
120533128  5,6-dihydroxyindole-2-carboxylic acid oxidase-like [KO:K00506] [EC:1.14.18.-]
120523790  dct; L-dopachrome tautomerase [KO:K01827] [EC:5.3.3.12]
120519910  edn1; endothelin-1 [KO:K16366]
120523771  endothelin receptor type B [KO:K04198]
120537178  endothelin receptor type B-like [KO:K04198]
120540294  guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
120525896  gnai3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
120533926  guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
120518946  plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
120539203  plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
120516316  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
120516513  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
120530526  calglandulin-like [KO:K02183]
120521606  calmodulin-like [KO:K02183]
120538670  calm3a; calmodulin 3a (phosphorylase kinase, delta) [KO:K02183]
120539370  calm3b; calmodulin 3b (phosphorylase kinase, delta) [KO:K02183]
120523494  calmodulin-alpha-like [KO:K02183]
120541657  calml4a; calmodulin-like protein 4a [KO:K02183]
120516414  calmodulin-alpha-like [KO:K02183]
120516454  calm2a; calmodulin 2a (phosphorylase kinase, delta) [KO:K02183]
120516564  calmodulin-like [KO:K02183]
120516565  calmodulin-like [KO:K02183]
120518519  calmodulin-1 [KO:K02183]
120538731  camk2g2; calcium/calmodulin-dependent protein kinase type II delta chain isoform X1 [KO:K04515] [EC:2.7.11.17]
120538827  calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
120533088  calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
120542230  camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
120517149  protein kinase C alpha type-like [KO:K02677] [EC:2.7.11.13]
120542651  prkcba; protein kinase C, beta a isoform X1 [KO:K19662] [EC:2.7.11.13]
120518916  protein kinase C alpha type-like 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
psex00350  Tyrosine metabolism
psex04010  MAPK signaling pathway
psex04310  Wnt signaling pathway
KO pathway
ko04916   
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