MEKK1 binds directly to the c-Jun N-terminal kinases/stress-activated protein kinases.
Mitogen-activated protein (MAP) kinases mediate responses to a wide array of cellular stimuli. These cascades consist of a MAP kinase or extracellular signal-regulated kinase (ERK), activated by a MAP/ERK kinase (MEK), in turn activated by a MEK kinase (MEKK). MEKK1 has been shown to be a strong activator of the c-Jun N-terminal kinase/stress-actived protein kinase (JNK/SAPK) pathway. We report here that JNK/SAPK binds directly to the N-terminal, noncatalytic domain of MEKK1 in vitro and in transfected cells. Immobilized MEKK1-derived peptides extract JNK/SAPK selectively from cell lysates. MEKK1 coimmunoprecipitates with multiple JNK/SAPK isoforms in transfected cells. Expression of the N terminus of MEKK1 lacking the kinase domain increases activation of endogenous JNK/SAPK by MEKK1. The data are consistent with a model in which MEKK1-JNK/SAPK binding facilitates the receipt of signals from upstream inputs and localizes JNK/SAPK to intracellular targets of the pathway.
Xu
S
S
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9041, USA.
Cobb
M H
MH
D000595:Amino Acid Sequence; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004285:Dogs; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D048728:MAP Kinase Kinase Kinase 1; D020928:Mitogen-Activated Protein Kinases; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011233:Precipitin Tests; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D013379:Substrate Specificity
D018076:DNA, Complementary; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human