Role of the amino-terminal domains of MEKKs in the activation of NF kappa B and MAPK pathways and in the regulation of cell proliferation and apoptosis.
Mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK) kinases (MEKKs) are serine/threonine kinases that are upstream regulators of MAPKs. Here, the role of the amino-terminal (N-terminal) domain of MEKK1-4 on the regulation of different intracellular signaling pathways, apoptosis, and cell proliferation has been assessed by comparing the responses induced by the full-length (FL) MEKKs to those induced by the kinase domains only. For each MEKK, the pattern of activation of NF kappa B, the ERK MAPK pathway, and the c-Jun N-terminal kinase (JNK) MAPK pathway markedly differed between the kinase domain and the FL form. Similarly, cell proliferation and apoptosis were differently regulated by the FL MEKK and the corresponding kinase domain. Our data show that the N-terminal domain of the MEKKs determines the specificity and the strength of activation of various intracellular signaling pathways and cellular responses.
Bonvin
Christelle
C
Institute of Cellular Biology and Morphology, Lausanne University, Lausanne, Switzerland.
Guillon
Audrey
A
van Bemmelen
Miguel X
MX
Gerwins
Pär
P
Johnson
Gary L
GL
Widmann
Christian
C
D017209:Apoptosis; D020134:Catalytic Domain; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D048728:MAP Kinase Kinase Kinase 1; D048730:MAP Kinase Kinase Kinase 2; D048748:MAP Kinase Kinase Kinase 3; D048768:MAP Kinase Kinase Kinase 4; D020930:MAP Kinase Kinase Kinases / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion
D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048728:MAP Kinase Kinase Kinase 1; D048730:MAP Kinase Kinase Kinase 2; D048748:MAP Kinase Kinase Kinase 3; D048768:MAP Kinase Kinase Kinase 4; D020930:MAP Kinase Kinase Kinases; C482576:MAP3K1 protein, human; C482618:MAP3K2 protein, human; C482625:MAP3K3 protein, human; C482779:MAP3K4 protein, human