KEGG   PATHWAY: mdo04916
Entry
mdo04916                    Pathway                                
Name
Melanogenesis - Monodelphis domestica (gray short-tailed opossum)
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
mdo04916  Melanogenesis
mdo04916

Organism
Monodelphis domestica (gray short-tailed opossum) [GN:mdo]
Gene
554192  POMC; proopiomelanocortin [KO:K05228]
100032347  ASIP; agouti signaling protein [KO:K08725]
100618641  MC1R; melanocortin 1 receptor [KO:K04199]
100021523  GNAS; GNAS complex locus [KO:K04632]
100029582  guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
100030463  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
100013164  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
100025332  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
100030872  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
100019274  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
100013823  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
100026554  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
100013831  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
100011211  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
100026861  PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100032298  cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100014049  CREB1; cAMP responsive element binding protein 1 [KO:K05870]
100017208  CREB3L2; cAMP responsive element binding protein 3 like 2 [KO:K09048]
100020067  CREB3L4; cAMP responsive element binding protein 3 like 4 [KO:K09048]
100022547  CREB3L3; cAMP responsive element binding protein 3 like 3 [KO:K09048]
100015046  CREB3L1; cAMP responsive element binding protein 3 like 1 [KO:K09048]
103104366  CREB3; cAMP responsive element binding protein 3 [KO:K09048]
100028102  EP300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
100013876  CREBBP; CREB binding protein [KO:K04498] [EC:2.3.1.48]
100020078  MITF; melanogenesis associated transcription factor [KO:K09455]
100032741  WNT1; Wnt family member 1 [KO:K03209]
100011991  WNT2; Wnt family member 2 [KO:K00182]
100033140  WNT2B; Wnt family member 2B [KO:K00182]
100024702  WNT3; Wnt family member 3 [KO:K00312]
100025651  WNT3A; Wnt family member 3A [KO:K00312]
100026048  WNT4; Wnt family member 4 [KO:K00408]
100012859  WNT5A; Wnt family member 5A [KO:K00444]
100021212  WNT5B; Wnt family member 5B [KO:K00444]
100010861  WNT6; Wnt family member 6 [KO:K00445]
100014091  WNT7B; Wnt family member 7B [KO:K00572]
100028905  WNT7A; Wnt family member 7A [KO:K00572]
100027787  WNT8B; Wnt family member 8B [KO:K00714]
100024816  WNT8A; Wnt family member 8A [KO:K00714]
100025627  WNT9A; Wnt family member 9A [KO:K01064]
100024657  WNT9B; Wnt family member 9B [KO:K01064]
100010973  WNT10A; Wnt family member 10A [KO:K01357]
100028529  WNT11; Wnt family member 11 [KO:K01384]
100012964  WNT16; Wnt family member 16 [KO:K01558]
100027981  FZD1; frizzled class receptor 1 [KO:K02432]
100019281  FZD7; frizzled class receptor 7 [KO:K02432]
100023490  FZD2; frizzled class receptor 2 [KO:K02235]
100030835  FZD3; frizzled class receptor 3 [KO:K02329]
100025855  FZD4; frizzled class receptor 4 [KO:K02354]
100016198  FZD5; frizzled class receptor 5 [KO:K02375]
100018016  FZD8; frizzled class receptor 8 [KO:K02375]
100023959  FZD6; frizzled class receptor 6 [KO:K02376]
100028967  FZD10; frizzled class receptor 10 [KO:K02842]
100029447  FZD9; frizzled class receptor 9 [KO:K02842]
100015137  GNAO1; G protein subunit alpha o1 [KO:K04534]
100011605  GNAQ; G protein subunit alpha q [KO:K04634]
100010047  DVL1; dishevelled segment polarity protein 1 [KO:K02353]
100022768  DVL3; dishevelled segment polarity protein 3 [KO:K02353]
100617787  DVL2; dishevelled segment polarity protein 2 [KO:K02353]
100012447  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
100022896  CTNNB1; catenin beta 1 [KO:K02105]
100017589  TCF7; transcription factor 7 (T-cell specific, HMG-box) [KO:K02620]
100030368  TCF7L1; transcription factor 7 like 1 [KO:K04490]
100021451  TCF7L2; transcription factor 7 like 2 [KO:K04491]
100011783  LEF1; lymphoid enhancer binding factor 1 [KO:K04492]
100021399  KITLG; KIT ligand [KO:K05461]
100017501  KIT; KIT proto-oncogene receptor tyrosine kinase [KO:K05091] [EC:2.7.10.1]
100032921  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
554186  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
554197  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
100022523  GTPase NRas-like [KO:K07828]
100015410  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
100018410  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100018044  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100028096  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100012916  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100010166  TYR; tyrosinase [KO:K00505] [EC:1.14.18.1]
100019721  TYRP1; tyrosinase related protein 1 [KO:K00506] [EC:1.14.18.-]
100027305  DCT; dopachrome tautomerase [KO:K01827] [EC:5.3.3.12]
100026601  EDN1; endothelin 1 [KO:K16366]
100013240  EDNRB; endothelin receptor type B [KO:K04198]
100013052  GNAI1; G protein subunit alpha i1 [KO:K04630]
100030095  GNAI3; G protein subunit alpha i3 [KO:K04630]
100032986  GNAI2; G protein subunit alpha i2 [KO:K04630]
100033281  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
100031660  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
100031869  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
100031263  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
100021688  CALM3; calmodulin 3 [KO:K02183]
100018191  CALM1; calmodulin 1 [KO:K02183]
100032171  CALM2; calmodulin 2 [KO:K02183]
100025795  CALML4; calmodulin like 4 [KO:K02183]
100015722  calmodulin-alpha-like [KO:K02183]
100022649  calmodulin-alpha-like [KO:K02183]
100011784  CAMK2D; calcium/calmodulin dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17]
100010898  CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
100024521  CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
100028973  CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
100024674  PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
100013346  PRKCB; protein kinase C beta [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
  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
mdo00350  Tyrosine metabolism
mdo04010  MAPK signaling pathway
mdo04310  Wnt signaling pathway
mdo05218  Melanoma
KO pathway
ko04916   
LinkDB

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