Entry Name Melanogenesis
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 systemBRITE hierarchy
Pathway map Ortholog table Orthology K08725 agouti signaling protein
K04199 melanocortin 1 receptor
K04632 guanine nucleotide-binding protein G(s) subunit alpha
K05870 cyclic AMP-responsive element-binding protein 1
K09048 cyclic AMP-responsive element-binding protein 3
K09455 microphthalmia-associated transcription factor
K03209 wingless-type MMTV integration site family, member 1
K00182 wingless-type MMTV integration site family, member 2
K00312 wingless-type MMTV integration site family, member 3
K00408 wingless-type MMTV integration site family, member 4
K00444 wingless-type MMTV integration site family, member 5
K00445 wingless-type MMTV integration site family, member 6
K00572 wingless-type MMTV integration site family, member 7
K00714 wingless-type MMTV integration site family, member 8
K01064 wingless-type MMTV integration site family, member 9
K01357 wingless-type MMTV integration site family, member 10
K01384 wingless-type MMTV integration site family, member 11
K01558 wingless-type MMTV integration site family, member 16
K04534 guanine nucleotide-binding protein G(o) subunit alpha
K04634 guanine nucleotide-binding protein G(q) subunit alpha
K02353 segment polarity protein dishevelled
K04490 transcription factor 7-like 1
K04491 transcription factor 7-like 2
K04492 lymphoid enhancer-binding factor 1
K04366 RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K00506 tyrosinase-related protein 1 [EC:1.14.18.-]
K04198 endothelin receptor type B
K04630 guanine nucleotide-binding protein G(i) subunit alpha
K04515 calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17 ]
Compound C01245 D-myo-Inositol 1,4,5-trisphosphate
Reference Authors Slominski A, Tobin DJ, Shibahara S, Wortsman J.
Title Melanin pigmentation in mammalian skin and its hormonal regulation.
Journal Reference Authors Busca R, Ballotti R.
Title Cyclic AMP a key messenger in the regulation of skin pigmentation.
Journal Reference Authors Imokawa G.
Title Autocrine and paracrine regulation of melanocytes in human skin and in pigmentary disorders.
Journal 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 Reference Authors Chin L.
Title The genetics of malignant melanoma: lessons from mouse and man.
Journal Reference Authors Miller AJ, Mihm MC Jr.
Title Melanoma.
Journal 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 Reference 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 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 Reference Authors Sturm RA, Teasdale RD, Box NF.
Title Human pigmentation genes: identification, structure and consequences of polymorphic variation.
Journal Reference Authors Hearing VJ.
Title The melanosome: the perfect model for cellular responses to the environment.
Journal 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 Related LinkDB All DBs
