KEGG   PATHWAY: mpah04916
mpah04916                   Pathway                                
Melanogenesis - Mus pahari (shrew mouse)
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.
Organismal Systems; Endocrine system
Pathway map
mpah04916  Melanogenesis

Mus pahari (shrew mouse) [GN:mpah]
110324728  Pomc; pro-opiomelanocortin [KO:K05228]
110319523  Asip; agouti-signaling protein [KO:K08725]
110337800  Mc1r; melanocyte-stimulating hormone receptor [KO:K04199]
110317699  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
110317700  neuroendocrine secretory protein 55 [KO:K04632]
110330584  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:]
110328764  Adcy2; adenylate cyclase type 2 [KO:K08042] [EC:]
110324646  Adcy3; adenylate cyclase type 3 [KO:K08043] [EC:]
110325439  Adcy4; adenylate cyclase type 4 [KO:K08044] [EC:]
110329393  Adcy5; adenylate cyclase type 5 [KO:K08045] [EC:]
110334500  Adcy6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:]
110337453  Adcy7; adenylate cyclase type 7 [KO:K08047] [EC:]
110334612  Adcy8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:]
110329624  Adcy9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:]
110337220  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:]
110320995  Prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:]
110322391  Creb1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
110320678  Creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
110316152  Creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
110326077  Creb3l3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
110338975  Creb3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
110318364  Creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
110334526  Ep300; histone acetyltransferase p300 [KO:K04498] [EC:]
110330048  Crebbp; CREB-binding protein isoform X1 [KO:K04498] [EC:]
110316879  Mitf; microphthalmia-associated transcription factor [KO:K09455]
110335204  Wnt1; proto-oncogene Wnt-1 [KO:K03209]
110316416  Wnt2; protein Wnt-2 [KO:K00182]
110320339  Wnt2b; protein Wnt-2b [KO:K00182]
110331952  Wnt3; proto-oncogene Wnt-3 [KO:K00312]
110331285  Wnt3a; protein Wnt-3a [KO:K00312]
110323343  Wnt4; protein Wnt-4 isoform X1 [KO:K00408]
110316538  Wnt5b; protein Wnt-5b [KO:K00444]
110325571  Wnt5a; protein Wnt-5a isoform X1 [KO:K00444]
110321884  Wnt6; protein Wnt-6 [KO:K00445]
110316305  Wnt7a; protein Wnt-7a [KO:K00572]
110335001  Wnt7b; protein Wnt-7b isoform X1 [KO:K00572]
110330357  Wnt8b; protein Wnt-8b [KO:K00714]
110333515  Wnt8a; protein Wnt-8a [KO:K00714]
110331284  Wnt9a; protein Wnt-9a isoform X1 [KO:K01064]
110332442  Wnt9b; protein Wnt-9b [KO:K01064]
110335137  Wnt10b; protein Wnt-10b isoform X1 [KO:K01357]
110322230  Wnt10a; protein Wnt-10a [KO:K01357]
110325401  Wnt11; protein Wnt-11 isoform X1 [KO:K01384]
110317136  Wnt16; protein Wnt-16 [KO:K01558]
110316646  Fzd1; frizzled-1 [KO:K02432]
110321753  Fzd7; frizzled-7 [KO:K02432]
110331922  Fzd2; frizzled-2 [KO:K02235]
110325524  Fzd3; frizzled-3 [KO:K02329]
110325899  Fzd4; frizzled-4 [KO:K02354]
110321741  Fzd5; frizzled-5 [KO:K02375]
110333155  Fzd8; frizzled-8 [KO:K02375]
110334890  Fzd6; frizzled-6 [KO:K02376]
110339184  Fzd10; frizzled-10 [KO:K02842]
110312856  Fzd9; frizzled-9 [KO:K02842]
110337832  Gnao1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
110336980  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
110329595  Dvl3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
110323116  Dvl1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
110331183  Dvl2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
110329614  Gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:]
110328516  Ctnnb1; catenin beta-1 isoform X1 [KO:K02105]
110332085  Tcf7; transcription factor 7 isoform X1 [KO:K02620]
110315696  Tcf7l1; transcription factor 7-like 1 isoform X1 [KO:K04490]
110313411  Tcf7l2; transcription factor 7-like 2 isoform X1 [KO:K04491]
110319903  Lef1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
110326225  Kitlg; kit ligand isoform X1 [KO:K05461]
110330230  Kit; mast/stem cell growth factor receptor Kit isoform X1 [KO:K05091] [EC:]
110318967  GTPase HRas-like isoform X1 [KO:K02833]
110319567  Hras; GTPase HRas [KO:K02833]
110338480  GTPase HRas-like [KO:K02833]
110333346  GTPase HRas-like [KO:K02833]
110316221  Kras; GTPase KRas isoform X1 [KO:K07827]
110320340  Nras; GTPase NRas [KO:K07828]
110314893  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:]
110327244  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:]
110326321  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:]
110329343  Mapk1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:]
110320020  Mapk3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:]
110327286  Tyr; tyrosinase isoform X1 [KO:K00505] [EC:]
110323788  Tyrp1; 5,6-dihydroxyindole-2-carboxylic acid oxidase [KO:K00506] [EC:1.14.18.-]
110325053  Dct; L-dopachrome tautomerase isoform X1 [KO:K01827] [EC:]
110334180  Edn1; endothelin-1 [KO:K16366]
110325338  Ednrb; endothelin B receptor [KO:K04198]
110314435  guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
110327202  Gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630]
110319821  Gnai3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
110336671  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:]
110317815  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:]
110318415  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:]
110319646  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:]
110328293  Calml4; calmodulin-like protein 4 isoform X1 [KO:K02183]
110334170  Calml3; calmodulin-like protein 3 [KO:K02183]
110334182  calmodulin-4 [KO:K02183]
110336102  Calm2; calmodulin isoform X1 [KO:K02183]
110324261  Calm1; calmodulin [KO:K02183]
110336466  Calm3; calmodulin [KO:K02183]
110331006  Camk2b; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:]
110320932  Camk2d; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:]
110332832  Camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:]
110325574  Camk2g; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:]
110332714  Prkca; protein kinase C alpha type isoform X1 [KO:K02677] [EC:]
110320075  Prkcb; protein kinase C beta type isoform X1 [KO:K19662] [EC:]
110336366  Prkcg; protein kinase C gamma type isoform X1 [KO:K19663] [EC:]
C00076  Calcium cation
C00082  L-Tyrosine
C00165  Diacylglycerol
C00575  3',5'-Cyclic AMP
C01245  D-myo-Inositol 1,4,5-trisphosphate
C05606  Melanin
Slominski A, Tobin DJ, Shibahara S, Wortsman J.
Melanin pigmentation in mammalian skin and its hormonal regulation.
Physiol Rev 84:1155-228 (2004)
Busca R, Ballotti R.
Cyclic AMP a key messenger in the regulation of skin pigmentation.
Pigment Cell Res 13:60-9 (2000)
Imokawa G.
Autocrine and paracrine regulation of melanocytes in human skin and in pigmentary disorders.
Pigment Cell Res 17:96-110 (2004)
Wikberg JE, Muceniece R, Mandrika I, Prusis P, Lindblom J, Post C, Skottner A.
New aspects on the melanocortins and their receptors.
Pharmacol Res 42:393-420 (2000)
Chin L.
The genetics of malignant melanoma: lessons from mouse and man.
Nat Rev Cancer 3:559-70 (2003)
Miller AJ, Mihm MC Jr.
N Engl J Med 355:51-65 (2006)
Saito H, Yasumoto K, Takeda K, Takahashi K, Yamamoto H, Shibahara S.
Microphthalmia-associated transcription factor in the Wnt signaling pathway.
Pigment Cell Res 16:261-5 (2003)
Imokawa G, Kobayashi T, Miyagishi M, Higashi K, Yada Y.
The role of endothelin-1 in epidermal hyperpigmentation and signaling mechanisms of mitogenesis and melanogenesis.
Pigment Cell Res 10:218-28 (1997)
Park HY, Gilchrest BA.
Signaling pathways mediating melanogenesis.
Cell Mol Biol (Noisy-le-grand) 45:919-30 (1999)
Park HY, Perez JM, Laursen R, Hara M, Gilchrest BA.
Protein kinase C-beta activates tyrosinase by phosphorylating serine residues in its cytoplasmic domain.
J Biol Chem 274:16470-8 (1999)
Sturm RA, Teasdale RD, Box NF.
Human pigmentation genes: identification, structure and consequences of polymorphic variation.
Gene 277:49-62 (2001)
Hearing VJ.
The melanosome: the perfect model for cellular responses to the environment.
Pigment Cell Res 13 Suppl 8:23-34 (2000)
Molina DM, Grewal S, Bardwell L.
Characterization of an ERK-binding domain in microphthalmia-associated transcription factor and differential inhibition of ERK2-mediated substrate phosphorylation.
J Biol Chem 280:42051-60 (2005)
mpah00350  Tyrosine metabolism
mpah04010  MAPK signaling pathway
mpah04310  Wnt signaling pathway
mpah05218  Melanoma
KO pathway

DBGET integrated database retrieval system