Abstract
ERK2 (extracellular-signal regulated kinase 2, also known as p42 mitogen-activated protein kinase) is an integral member of the mitogen-activated protein kinase cascade that is crucial for many cellular events such as proliferation and differentiation. Here, we determined the genomic organization of the Erk2 gene and characterized its promoter. The Erk2 gene spans over 60 kilobases, and the coding region is split into eight exons. In the coding region, exon-intron organization was exactly conserved between the two mouse genes for ERK2 and ERK1 except one junction shifted by one nucleotide. Primer extension and S1 nuclease analyses identified two major transcription start sites located at -219 and -223 relative to the translation start site. The 5'-flanking sequence lacked TATA box but contained a CCAAT box located approximately 60 base pairs upstream of transcription start sites. Sequencing of the 5'-flanking region also revealed potential cis-acting elements for multiple transcriptional regulatory factors including Sp1, zif268, Ets, CREB, and PuF sites. The promoter activity of the 5'-flanking region was examined using chloramphenicol acetyltransferase as a reporter gene. Transient transfection experiments using Chinese hamster ovary cells defined a maximal promoter activity in a 371-base pair region immediately upstream of the translation start site. Furthermore, we demonstrated, using mouse P19 embryonal carcinoma cells, that this 371-base pair sequence is likely to be sufficient to confer the transcriptional activation of the ERK2 promoter during the retinoic acid-induced differentiation of P19 cells.
Highlights
The mitogen-activated protein (MAP)1 kinase cascade is activated by a myriad of proliferation- and differentiation-inducing stimuli [1,2,3,4,5,6]
Exon-intron organization was exactly conserved between the two mouse genes for ERK2 and ERK1 except one junction shifted by one nucleotide
We demonstrated, using mouse P19 embryonal carcinoma cells, that this 371base pair sequence is likely to be sufficient to confer the transcriptional activation of the ERK2 promoter during the retinoic acid-induced differentiation of P19 cells
Summary
ERK1 (extracellular signal-regulated kinase 1) and ERK2, known as 44- and 42 kDa-protein, respectively, were the first vertebrate MAP kinases to be described [7,8,9] and are the most closely related isoforms among the increasing MAP kinase multigene family [10] sharing approximately 90% identity in the amino acid sequence [9] These two kinases are similar in many aspects, such as ubiquitous tissue distribution [9, 11, 12], sensitivity to activation by MEK [13], and substrate specificity [2].
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