Evidence for a role of MEK and MAPK during signal transduction by protein kinase C zeta.

TitleEvidence for a role of MEK and MAPK during signal transduction by protein kinase C zeta.
Publication TypeJournal Article
Year of Publication1995
AuthorsBerra E, Diaz-Meco MT, Lozano J, Frutos S, Municio MM, Sanchez P, Sanz L, Moscat J
JournalEMBO J
Date Published1995 Dec 15
KeywordsAnimals, Base Sequence, Calcium-Calmodulin-Dependent Protein Kinases, Cell Line, Cell Nucleus, DNA, Enzyme Activation, Mitogen-Activated Protein Kinase Kinases, Mitosis, Molecular Sequence Data, Mutation, NF-kappa B, Promoter Regions, Genetic, Protein Kinase C, Protein Kinases, Signal Transduction, Tumor Necrosis Factor-alpha

Protein kinase C zeta (zeta PKC) is critically involved in the control of a number of cell functions, including proliferation and nuclear factor kappa B (NF-kappa B) activation. Previous studies indicate that zeta PKC is an important step downstream of Ras in the mitogenic cascade. The stimulation of Ras initiates a kinase cascade that culminates in the activation of MAP kinase (MAPK), which is required for cell growth. MAPK is activated by phosphorylation by another kinase named MAPK kinase (MEK), which is the substrate of a number of Ras-activated serine/threonine kinases such as c-Raf-1 and B-Raf. We show here that MAPK and MEK are activated in vivo by an active mutant of zeta PKC, and that a kinase-defective dominant negative mutant of zeta PKC dramatically impairs the activation of both MEK and MAPK by serum and tumour necrosis factor (TNF alpha). The stimulation of other kinases, such as stress-activated protein kinase (SAPK) or p70S6K, is shown here to be independent of zeta PKC. The importance of MEK/MAPK in the signalling mechanisms activated by zeta PKC was addressed by using the activation of a kappa B-dependent promoter as a biological read-out of zeta PKC.

Alternate JournalEMBO J
PubMed ID8557035
PubMed Central IDPMC394740
Related Faculty: 
Jorge Moscat, Ph.D. Maria Diaz-Meco Conde, Ph.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700