KEGG   PATHWAY: rno04916
Entry
rno04916                    Pathway                                
Name
Melanogenesis - Rattus norvegicus (rat)
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
rno04916  Melanogenesis
rno04916

Organism
Rattus norvegicus (rat) [GN:rno]
Gene
24664  Pomc; pro-opiomelanocortin precursor [KO:K05228]
102552838  Mc1r; melanocyte-stimulating hormone receptor [KO:K04199]
24896  Gnas; SCG6 (secretogranin VI) isoform SCG6 precursor [KO:K04632]
305509  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
81636  Adcy2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
64508  Adcy3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
54223  Adcy4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
64532  Adcy5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
25289  Adcy6; adenylate cyclase type 6 isoform 2 [KO:K08046] [EC:4.6.1.1]
84420  Adcy7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
29241  Adcy8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
302950  Adcy9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
25636  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
293508  Prkacb; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
81646  Creb1; cyclic AMP-responsive element-binding protein 1 isoform A [KO:K05870]
310616  Creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform 1 [KO:K09048]
362165  Creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
362339  Creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
314638  Creb3l3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
54244  Crebbp; histone lysine acetyltransferase CREBBP [KO:K04498] [EC:2.3.1.48]
170915  Ep300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
25094  Mitf; microphthalmia-associated transcription factor isoform 1 [KO:K09455]
24881  Wnt1; proto-oncogene Wnt-1 precursor [KO:K03209]
116466  Wnt2b; protein Wnt-2b [KO:K00182]
114487  Wnt2; protein Wnt-2 precursor [KO:K00182]
24882  Wnt3; proto-oncogene Wnt-3 [KO:K00312]
303181  Wnt3a; protein Wnt-3a precursor [KO:K00312]
84426  Wnt4; protein Wnt-4 precursor [KO:K00408]
64566  Wnt5a; protein Wnt-5a precursor [KO:K00444]
282582  Wnt5b; protein Wnt-5b precursor [KO:K00444]
316526  Wnt6; protein Wnt-6 precursor [KO:K00445]
114850  Wnt7a; protein Wnt-7a precursor [KO:K00572]
315196  Wnt7b; protein Wnt-7b isoform 1 [KO:K00572]
291678  Wnt8a; protein Wnt-8a precursor [KO:K00714]
293990  Wnt8b; protein Wnt-8b precursor [KO:K00714]
287357  Wnt9a; protein Wnt-9a precursor [KO:K01064]
303586  Wnt9b; protein Wnt-9b precursor [KO:K01064]
315294  Wnt10b; protein Wnt-10b precursor [KO:K01357]
316527  Wnt10a; protein Wnt-10a precursor [KO:K01357]
140584  Wnt11; protein Wnt-11 [KO:K01384]
500047  Wnt16; protein Wnt-16 precursor [KO:K01558]
58868  Fzd1; frizzled-1 precursor [KO:K02432]
100360552  Fzd7; frizzled-7 precursor [KO:K02432]
64512  Fzd2; frizzled-2 precursor [KO:K02235]
266715  Fzd3; frizzled-3 precursor [KO:K02329]
64558  Fzd4; frizzled-4 precursor [KO:K02354]
317674  Fzd5; frizzled-5 precursor [KO:K02375]
364754  Fzd8; frizzled-8 precursor [KO:K02375]
282581  Fzd6; frizzled-6 precursor [KO:K02376]
266608  Fzd9; frizzled-9 precursor [KO:K02842]
363913  Fzd10; frizzled-10 precursor [KO:K02842]
50664  Gnao1; guanine nucleotide-binding protein G(o) subunit alpha isoform B [KO:K04534]
81666  Gnaq; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
83721  Dvl1; segment polarity protein dishevelled homolog DVL-1 [KO:K02353]
303811  Dvl3; segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
303251  Dvl2; segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
84027  Gsk3b; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
84353  Ctnnb1; catenin beta-1 [KO:K02105]
363595  Tcf7; transcription factor 7 [KO:K02620]
312451  Tcf7l1; transcription factor 7-like 1 [KO:K04490]
679869  Tcf7l2; transcription factor 7-like 2 [KO:K04491]
161452  Lef1; lymphoid enhancer-binding factor 1 [KO:K04492]
60427  Kitlg; kit ligand isoform 1 precursor [KO:K05461]
64030  Kit; mast/stem cell growth factor receptor Kit precursor [KO:K05091] [EC:2.7.10.1]
293621  Hras; GTPase HRas [KO:K02833]
367858  Hrasl1; HRas proto-oncogene, GTPase like 1 [KO:K02833]
24525  Kras; GTPase KRas [KO:K07827]
24605  Nras; GTPase NRas [KO:K07828]
24703  Raf1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
170851  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
58960  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
116590  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
50689  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
308800  Tyr; tyrosinase precursor [KO:K00505] [EC:1.14.18.1]
298182  Tyrp1; 5,6-dihydroxyindole-2-carboxylic acid oxidase precursor [KO:K00506] [EC:1.14.18.-]
290484  Dct; dopachrome tautomerase precursor [KO:K01827] [EC:5.3.3.12]
24323  Edn1; endothelin-1 preproprotein [KO:K16366]
50672  Ednrb; endothelin receptor type B precursor [KO:K04198]
25686  Gnai1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
25643  Gnai3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
81664  Gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
24654  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
29322  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
85240  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
25031  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
364774  Calml5; calmodulin-like protein 5 [KO:K02183]
307100  Calml3; calmodulin-like protein 3 [KO:K02183]
691455  Calml4; calmodulin-like protein 4 [KO:K02183]
24242  Calm1; calmodulin-1 [KO:K02183]
24244  Calm3; calmodulin-3 [KO:K02183]
50663  Calm2; calmodulin-2 [KO:K02183]
25400  Camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
24246  Camk2d; calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]
24245  Camk2b; calcium/calmodulin-dependent protein kinase type II subunit beta isoform 2 [KO:K04515] [EC:2.7.11.17]
171140  Camk2g; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
24680  Prkca; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
25023  Prkcb; protein kinase C beta type isoform 2 [KO:K19662] [EC:2.7.11.13]
24681  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
rno00350  Tyrosine metabolism
rno04010  MAPK signaling pathway
rno04310  Wnt signaling pathway
rno05218  Melanoma
KO pathway
ko04916   
LinkDB

DBGET integrated database retrieval system