The Elk-1 ETS-domain transcription factor contains a mitogen-activated protein kinase targeting motif.
The phosphorylation of transcription factors by mitogen-activated protein kinases (MAP) is a pivotal event in the cellular response to the activation of MAP kinase signal transduction pathways. Mitogenic and stress stimuli activate different pathways and lead to the activation of distinct groups of target proteins. Elk-1 is targeted by three distinct MAP kinase pathways. In this study, we demonstrate that the MAP kinase ERK2 is targeted to Elk-1 by a domain which is distinct from, and located N-terminally to, its phosphoacceptor motifs. Targeting via this domain is essential for the efficient and rapid phosphorylation of Elk-1 in vitro and full and rapid activation in vivo. Specific residues involved in ERK targeting have been identified. Our data indicate that the targeting of different classes of MAP kinases to their nuclear substrates may be a common mechanism to increase the specificity and efficiency of this signal transduction pathway.
Yang
S H
SH
Department of Biochemistry and Genetics, The Medical School, University of Newcastle upon Tyne, United Kingdom.
Yates
P R
PR
Whitmarsh
A J
AJ
Davis
R J
RJ
Sharrocks
A D
AD
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D015003:Yeasts; D050807:ets-Domain Protein Elk-1
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D020794:Receptor Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1