Activation of the Sap-1a transcription factor by the c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase.
Ternary complex factors (TCFs) bind to the serum response element in the c-fos promoter and mediate its activation by many extracellular stimuli. Some of these stimuli activate the ERK subclass of mitogen-activated protein kinases (MAPKs) that target the TCF Sap-1a. We show that Sap-1a is also phosphorylated by the stress-activated JNK subclass of MAPKs leading to stimulation of both c-fos serum response element and E74-site-dependent transcription in RK13 cells. Several JNK-1 phosphorylation sites were mapped within Sap-1a, and mutation of these sites affected the transactivation mediated by Sap-1a and JNK-1. The impact of these phosphorylation sites varied at different promoters and was dependent on whether Sap-1a was stimulated by ERK-1 or JNK-1. Additionally, a comparison of Sap-1a with another TCF, Elk-1, revealed that these proteins behaved differently to stimulation by ERK-1 and JNK-1. Furthermore, activation of Sap-1a by JNK-1 was inhibited by the p38(MAPK) in RK13 cells, possibly by competition for a common upstream activator. Altogether, our data suggest that Sap-1a plays an important role in the nuclear response elicited by cellular stress.
Janknecht
R
R
Molecular Biology and Virology Laboratory, The Salk Institute, La Jolla, California 92037, USA.
Hunter
T
T
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism*; D011817:Rabbits; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D050808:ets-Domain Protein Elk-4; D048051:p38 Mitogen-Activated Protein Kinases
D004268:DNA-Binding Proteins; D047428:Protein Kinase Inhibitors; D014157:Transcription Factors; D050808:ets-Domain Protein Elk-4; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases