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 cel lular differentiation and/or proliferation in a wide variety of cell types, including developing thymocytes. The basic helix-loop-helix (bHLH) protein s E12 and E47 and an inhibitor HLH protein, Id3, play key roles in thymocyt e 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 a re rapidly induced upon signaling from the TCR. Activation of Id3 transcrip tion is regulated in a dose-dependent manner by the extracellular signal-re gulated kinase (ERK) MAPK module. These observations directly connect the E RK MAPK cascade and HLH proteins in a linear pathway.