Reactome | GSK3B phosphorylates p-S409 MITF-M at S397, S401 and S405

GSK3B phosphorylates p-S409 MITF-M at S397, S401 and S405

Stable Identifier

R-HSA-9824995

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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GSK3B phosphorylates p-S409 MITF-M at S397, S401 and S405

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RPS6KA1-dependent phosphorylation of MITF-M at serine 409 primes the protein for subsequent phosphorylations at three sites in the C-terminal region by GSK3B. Mutation of serine residues at S397, S401 and S405 to alanine increases the stability of MITF-M, suggesting a role for GSK3B in degradation of the protein. Consistent with this, WNT3A treatment, which inactivates GSK3B, increases MITF-M stability and increases its transcription factor activity towards target gene MART1 in the melanoma cell line M308 (Wu et al, 2000; Ploper et al, 2015; reviewed in Goding and Arnheiter, 2019). Note however that this effect may also be the result of WNT3A-dependent abrogation of GSK3B-dependent phosphorylation at S69 and subsequent nuclear export, as described (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
25605940	MITF drives endolysosomal biogenesis and potentiates Wnt signaling in melanoma cells Graeber, TG, Perez, BS, von Euw, E, Ploper, D, Ribas, A, Taelman, VF, Titz, B, Robert, L, De Robertis, EM, Chen, HW	Proc Natl Acad Sci U S A	2015