GSK3B phosphorylates p-S73 MITF-M at residue S69

Stable Identifier
R-HSA-9824999
Type
Reaction [transition]
Species
Homo sapiens
Compartment
nucleoplasm
ReviewStatus
5/5
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GSK3B phosphorylates p-S73 MITF-M at residue S69
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MAPK-dependent phosphorylation of MITF-M at serine 73 is a priming event for subsequent phosphorylation by GSK3B at serine 69. Phosphorylation at serine 69 in turn targets MITF-M for XPO1 (also known as CRM1)-based nuclear export, limiting the transcription factor activity of MITF-M (Hemesath et al, 1998; Ngeow et al, 2018; reviewed in Goding and Arnheiter, 2019). Expression of a plasmid encoding MITFA S69A, but not the phosphomimetic S69E, rescues melanophore development in mitfa-null nacre zebrafish embryos, highlighting the critical role of phosphorylation at this site for melanocyte development (Ngeow et al, 2018).
Literature References
PubMed ID Title Journal Year
31123060 MITF-the first 25 years

Arnheiter, H, Goding, CR

Genes Dev 2019
10673502 c-Kit triggers dual phosphorylations, which couple activation and degradation of the essential melanocyte factor Mi

Hemesath, TJ, Fisher, DE, Wells, AG, Fisher, DZ, Wu, M, Takemoto, CM, Horstmann, MA, Price, ER

Genes Dev 2000
30150413 BRAF/MAPK and GSK3 signaling converges to control MITF nuclear export

Knapp, S, Patton, EE, Friedrichsen, HJ, Berridge, G, Filippakopoulos, P, Andrews, S, Fischer, R, Goding, CR, Picaud, S, Brunsdon, H, Ngeow, KC, Borden, KLB, Zeng, Z, Steingrímsson, E, Lisle, R, Knowles, H, Volpon, L, Li, L

Proc Natl Acad Sci U S A 2018
9440696 MAP kinase links the transcription factor Microphthalmia to c-Kit signalling in melanocytes

Hemesath, TJ, Fisher, DE, Takemoto, C, Badalian, T, Price, ER

Nature 1998
Participants
Input
Output
Participates
as an event of
Catalyst Activity

protein serine/threonine kinase activity of GSK3B [nucleoplasm]

Physical Entity
GSK3B [nucleoplasm] (Homo sapiens)
Activity
protein serine/threonine kinase activity (GO:0004674)
Orthologous Events
GSK3B phosphorylates p-S73 MITF-M at residue S69 (Bos taurus)
GSK3B phosphorylates p-S73 MITF-M at residue S69 (Caenorhabditis elegans)
GSK3B phosphorylates p-S73 MITF-M at residue S69 (Canis familiaris)
GSK3B phosphorylates p-S73 MITF-M at residue S69 (Drosophila melanogaster)
GSK3B phosphorylates p-S73 MITF-M at residue S69 (Gallus gallus)
GSK3B phosphorylates p-S73 MITF-M at residue S69 (Mus musculus)
GSK3B phosphorylates p-S73 MITF-M at residue S69 (Rattus norvegicus)
GSK3B phosphorylates p-S73 MITF-M at residue S69 (Saccharomyces cerevisiae)
GSK3B phosphorylates p-S73 MITF-M at residue S69 (Sus scrofa)
Authored
Rothfels, K  (2023-01-26)
Reviewed
de la Serna, IL  (2024-05-21)
Arnheiter, H  (2024-02-26)
Created
Rothfels, K  (2023-01-23)
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