PMID- 10587587
OWN - NLM
STAT- MEDLINE
DCOM- 20000229
LR  - 20190513
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 9
IP  - 1
DP  - 2000 Jan 1
TI  - Ser298 of MITF, a mutation site in Waardenburg syndrome type 2, is a
      phosphorylation site with functional significance.
PG  - 125-32
AB  - MITF (microphthalmia-associated transcription factor) is a
      basic-helix-loop-helix-leucine zipper (bHLHZip) factor which regulates expression
      of tyrosinase and other melanocytic genes via a CATGTG promoter sequence, and is 
      involved in melanocyte differentiation. Mutations of MITF in mice or humans with 
      Waardenburg syndrome type 2 (WS2) often severely disrupt the bHLHZip domain,
      suggesting the importance of this structure. Here, we show that Ser298, which
      locates downstream of the bHLHZip and was previously found to be mutated in
      individuals with WS2, plays an important role in MITF function. Glycogen synthase
      kinase 3 (GSK3) was found to phosphorylate Ser298 in vitro, thereby enhancing the
      binding of MITF to the tyrosinase promoter. The same serine was found to be
      phosphorylated in vivo, and expression of dominant-negative GSK3beta selectively 
      suppressed the ability of MITF to transactivate the tyrosinase promoter.
      Moreover, mutation of Ser298, as found in a WS2 family, disabled phos-phorylation
      of MITF by GSK3beta and impaired MITF function. These findings suggest that the
      Ser298 is important for MITF function and is phosphorylated probably by GSK3beta.
FAU - Takeda, K
AU  - Takeda K
AD  - Department of Molecular Biology and Applied Physiology, Tohoku University School 
      of Medicine, Sendai 980-8575, Japan.
FAU - Takemoto, C
AU  - Takemoto C
FAU - Kobayashi, I
AU  - Kobayashi I
FAU - Watanabe, A
AU  - Watanabe A
FAU - Nobukuni, Y
AU  - Nobukuni Y
FAU - Fisher, D E
AU  - Fisher DE
FAU - Tachibana, M
AU  - Tachibana M
LA  - eng
GR  - AR43369/AR/NIAMS NIH HHS/United States
GR  - KO8 HL3700/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (MITF protein, human)
RN  - 0 (Microphthalmia-Associated Transcription Factor)
RN  - 0 (Mitf protein, mouse)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Transcription Factors)
RN  - 452VLY9402 (Serine)
RN  - EC 1.14.18.1 (Monophenol Monooxygenase)
RN  - EC 2.7.11.- (Glycogen Synthase Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
MH  - Amino Acid Substitution
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinases/metabolism
MH  - Cell Line
MH  - DNA-Binding Proteins/*genetics/*metabolism
MH  - Genes, Dominant
MH  - Glycogen Synthase Kinase 3
MH  - Glycogen Synthase Kinases
MH  - Helix-Loop-Helix Motifs
MH  - Humans
MH  - Mice
MH  - Microphthalmia-Associated Transcription Factor
MH  - Monophenol Monooxygenase/genetics/metabolism
MH  - *Mutation
MH  - Phosphorylation
MH  - Recombinant Proteins/genetics/metabolism
MH  - Sequence Deletion
MH  - Serine/genetics/metabolism
MH  - Transcription Factors/genetics/metabolism
MH  - Transcriptional Activation
MH  - Waardenburg Syndrome/*genetics
EDAT- 1999/12/10 09:00
MHDA- 2000/03/04 09:00
CRDT- 1999/12/10 09:00
PHST- 1999/12/10 09:00 [pubmed]
PHST- 2000/03/04 09:00 [medline]
PHST- 1999/12/10 09:00 [entrez]
AID - ddd010 [pii]
AID - 10.1093/hmg/9.1.125 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2000 Jan 1;9(1):125-32. doi: 10.1093/hmg/9.1.125.