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 Orthology K00182 WNT2; wingless-type MMTV integration site family, member 2
K00312 WNT3; wingless-type MMTV integration site family, member 3
K00408 WNT4; wingless-type MMTV integration site family, member 4
K00444 WNT5; wingless-type MMTV integration site family, member 5
K00445 WNT6; wingless-type MMTV integration site family, member 6
K00506 TYRP1; tyrosinase-related protein 1 [EC:1.14.18.-]
K00572 WNT7; wingless-type MMTV integration site family, member 7
K00714 WNT8; wingless-type MMTV integration site family, member 8
K01064 WNT9; wingless-type MMTV integration site family, member 9
K01357 WNT10; wingless-type MMTV integration site family, member 10
K01384 WNT11; wingless-type MMTV integration site family, member 11
K01558 WNT16; wingless-type MMTV integration site family, member 16
K02353 DVL; segment polarity protein dishevelled
K02354 FZD4, fz4, CD344; frizzled 4
K02375 FZD5_8, fz2; frizzled 5/8
K02432 FZD1_7, fz; frizzled 1/7
K02620 TCF7, TCF-1; transcription factor 7
K02842 FZD9_10, CD349_50; frizzled 9/10
K03209 WNT1; wingless-type MMTV integration site family, member 1
K04198 EDNRB; endothelin receptor type B
K04199 MC1R; melanocortin 1 receptor
K04366 RAF1; RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04368 MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2 ]
K04369 MAP2K2, MEK2; mitogen-activated protein kinase kinase 2 [EC:2.7.12.2 ]
K04490 TCF7L1; transcription factor 7-like 1
K04491 TCF7L2; transcription factor 7-like 2
K04492 LEF1; lymphoid enhancer-binding factor 1
K04515 CAMK2; calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17 ]
K04534 GNAO, G-ALPHA-O; guanine nucleotide-binding protein G(o) subunit alpha
K04630 GNAI; guanine nucleotide-binding protein G(i) subunit alpha
K04632 GNAS; guanine nucleotide-binding protein G(s) subunit alpha
K04634 GNAQ; guanine nucleotide-binding protein G(q) subunit alpha
K05091 KIT, SCFR, CD117; proto-oncogene tyrosine-protein kinase Kit [EC:2.7.10.1 ]
K05228 POMC; proopiomelanocortin
K05870 CREB1; cyclic AMP-responsive element-binding protein 1
K07827 KRAS, KRAS2; GTPase KRas
K08725 ASIP; agouti signaling protein
K09048 CREB3; cyclic AMP-responsive element-binding protein 3
K09455 MITF; microphthalmia-associated transcription factor
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
