PMID- 10527940
OWN - NLM
STAT- MEDLINE
DCOM- 20000103
LR  - 20181201
IS  - 0264-6021 (Print)
IS  - 0264-6021 (Linking)
VI  - 343 Pt 3
DP  - 1999 Nov 1
TI  - Mitogen-activated protein kinase mediates erythropoietin-induced phosphorylation 
      of the TAL1/SCL transcription factor in murine proerythroblasts.
PG  - 615-20
AB  - Ectopic expression of the basic helix-loop-helix transcription factor TAL1 (or
      SCL) is the most frequent gain-of-function mutation in T-cell acute lymphoblastic
      leukaemia. Gene-knockout studies in mice have demonstrated that TAL1 is required 
      for embryonic and adult haematopoiesis, and considerable evidence suggests it
      also has important functions in terminal erythroid differentiation. We reported
      previously that TAL1 phosphorylation is stimulated by erythropoietin in splenic
      proerythroblasts isolated from mice infected with the anaemia-inducing strain of 
      Friend virus and show here the signalling pathway responsible. Erythropoietin was
      found to stimulate nuclear mitogen-activated protein kinase activity in addition 
      to TAL1 protein phosphorylation, both of which were quantitatively inhibited by
      the mitogen-activated protein kinase kinase inhibitor PD 098059 and the
      phosphatidylinositol 3-kinase inhibitor wortmannin. Tryptic phosphopeptide
      analysis of radiolabelled TAL1 immunoprecipitated from nuclear extracts of Friend
      virus-induced proerythroblasts revealed that phosphorylation of Ser(122), shown
      previously to be a substrate for the mitogen-activated protein kinase ERK1
      (extracellular signal-regulated protein kinase) in vitro, was specifically,
      although not exclusively, increased by erythropoietin and inhibited by wortmannin
      and PD 098059. These results are consistent with an erythropoietin-stimulated
      signalling pathway in which there is direct activation of a mitogen-activated
      protein kinase kinase by phosphatidylinositol 3-kinase and identify TAL1 as one
      of its nuclear targets. These data suggest, in addition, a specific mechanism by 
      which the principal regulator of erythroid differentiation could enhance TAL1
      function, in addition to increasing its expression.
FAU - Tang, T
AU  - Tang T
AD  - Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
      37232, USA.
FAU - Prasad, K S
AU  - Prasad KS
FAU - Koury, M J
AU  - Koury MJ
FAU - Brandt, S J
AU  - Brandt SJ
LA  - eng
GR  - R01 HL49118/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Androstadienes)
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (Phosphopeptides)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (T-Cell Acute Lymphocytic Leukemia Protein 1)
RN  - 0 (Tal1 protein, mouse)
RN  - 0 (Transcription Factors)
RN  - 17885-08-4 (Phosphoserine)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - Androstadienes/pharmacology
MH  - Anemia/metabolism/virology
MH  - Animals
MH  - Basic Helix-Loop-Helix Transcription Factors
MH  - DNA-Binding Proteins/chemistry/*metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Erythroblasts/*metabolism
MH  - Flavonoids/pharmacology
MH  - Friend murine leukemia virus
MH  - Hematopoietic Stem Cells/*metabolism
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Mutagenesis, Site-Directed
MH  - Phosphopeptides/chemistry/isolation & purification
MH  - Phosphorylation
MH  - Phosphoserine/analysis
MH  - *Proto-Oncogene Proteins
MH  - Recombinant Proteins/metabolism
MH  - Spleen
MH  - T-Cell Acute Lymphocytic Leukemia Protein 1
MH  - Transcription Factors/metabolism
MH  - Wortmannin
PMC - PMC1220593
EDAT- 1999/10/21 00:00
MHDA- 1999/10/21 00:01
CRDT- 1999/10/21 00:00
PHST- 1999/10/21 00:00 [pubmed]
PHST- 1999/10/21 00:01 [medline]
PHST- 1999/10/21 00:00 [entrez]
PST - ppublish
SO  - Biochem J. 1999 Nov 1;343 Pt 3:615-20.