Regulation of the helix-loop-helix proteins, E2A and Id3, by the Ras-ERK MAPK cascade.
Activation of mitogen-activated protein kinase (MAPK) pathways leads to cellular differentiation and/or proliferation in a wide variety of cell types, including developing thymocytes. The basic helix-loop-helix (bHLH) proteins E12 and E47 and an inhibitor HLH protein, Id3, play key roles in thymocyte differentiation. We show here that E2A DNA binding is lowered in primary immature thymocytes consequent to T cell receptor (TCR)-mediated ligation. Whereas expression of E2A mRNA and protein are unaltered, Id3 transcripts are rapidly induced upon signaling from the TCR. Activation of Id3 transcription is regulated in a dose-dependent manner by the extracellular signal-regulated kinase (ERK) MAPK module. These observations directly connect the ERK MAPK cascade and HLH proteins in a linear pathway.
Bain
G
G
Department of Biology, 0366, University of California at San Diego, La Jolla, CA 92093, USA.
Cravatt
C B
CB
Loomans
C
C
Alberola-Ila
J
J
Hedrick
S M
SM
Murre
C
C
D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051766:Early Growth Response Protein 1; D004789:Enzyme Activation; D018257:Helix-Loop-Helix Motifs; D017874:Immediate-Early Proteins; D051796:Inhibitor of Differentiation Proteins; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D048369:MAP Kinase Kinase 1; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009363:Neoplasm Proteins; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D018631:ras Proteins / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D051796:Inhibitor of Differentiation Proteins; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D009363:Neoplasm Proteins; D017346:Protein Serine-Threonine Kinases; D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors; D018631:ras Proteins; C486109:Egr1 protein, mouse; C407909:TCF3 protein, human; C075640:ID3 protein, human; C482125:MAP2K1 protein, human; C482127:Map2k1 protein, mouse