The MAP kinase phosphorylation site of TAL1 occurs within a transcriptional activation domain.
Alteration of the TAL1 gene is the most common genetic lesion found in patients with T cell acute lymphoblastic leukemia. TAL1 encodes a basic helix-loop-helix transcription factor that is phosphorylated on serine residue 122 by the mitogen-activated protein (MAP) kinase ERK1. Here we show that the amino-terminal sequences of TAL1 (residues 1-166) function in vivo as a transcriptional activation domain. Mutation of serine residue 122 reduces the potency of the transactivation domain by more than half. The data suggest that the amino-terminal transactivation domain of TAL1 is positively regulated by S122 phosphorylation and that the functional properties of TAL1 can be influenced by signal transduction pathways that involve the MAP kinases.
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235.
I A
IA
Wadman
H L
HL
Hsu
M H
MH
Cobb
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R
Baer
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins; D015398:Signal Transduction; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; D015533:Transcriptional Activation
D051792:Basic Helix-Loop-Helix Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D004268:DNA-Binding Proteins; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C067143:TAL1 protein, human