Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms

  title={Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms},
  author={Benoît Dérijard and Joel Raingeaud and Tamera Barrett and I-Huan Wu and J M Han and RJ Ulevitch and RJ Davis},
  pages={682 - 685}
Mammalian mitogen-activated protein (MAP) kinases include extracellular signal-regulated protein kinase (ERK), c-Jun amino-terminal kinase (JNK), and p38 subgroups. These MAP kinase isoforms are activated by dual phosphorylation on threonine and tyrosine. Two human MAP kinase kinases (MKK3 and MKK4) were cloned that phosphorylate and activate p38 MAP kinase. These MKK isoforms did not activate the ERK subgroup of MAP kinases, but MKK4 did activate JNK. These data demonstrate that the activators… 

Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase.

The molecular cloning of a new member of the mammalian MAP kinase kinase group (MKK7) that functions as an activator of JNK is reported, established to be a novel component of the JNK signal transduction pathway.

Phosphorylation of MAP Kinases by MAP/ERK Involves Multiple Regions of MAP Kinases*

Experimental results and modeling support the conclusion that the specificity of MEK/MAP kinase phosphorylation results from multiple contacts, including surfaces in both the N- and C-terminal domains.

Transcription factor AP-1 regulation by mitogen-activated protein kinase signal transduction pathways

Recent progress towards understanding AP-1 regulation by the ERK, JNK, and p38 MAP kinase signal transduction pathways is reviewed.

Identification of a dual specificity kinase that activates the Jun kinases and p38-Mpk2.

A dual-specificity kinase that activates JNK, named JNKK, was identified that functions between MEKK and JNK and was unresponsive to Raf-1 in transfected HeLa cells.

Selective Activation of p38 Mitogen-activated Protein (MAP) Kinase Isoforms by the MAP Kinase Kinases MKK3 and MKK6*

The molecular cloning of a novel isoform of p38 MAP kinase, p38β2, is reported, which, like p38α, is inhibited by the pyridinyl imidazole drug SB203580.

Molecular Cloning of Mitogen-activated Protein/ERK Kinase Kinases (MEKK) 2 and 3

A family of MEKK proteins capable of regulating sequential protein kinase pathways involving MAPK members is defined, which includes MEKK 2, MEK 1, and JNK kinase.

Actions of Rho family small G proteins and p21-activated protein kinases on mitogen-activated protein kinase family members

It is found that overexpression of the Ste20-related enzymes p21-activated kinase 1 (PAK1) and PAK2 in 293 cells is sufficient to activate JNK/SAPK and to a lesser extent p38 MAP kinase but not ERK2, suggesting a permissive role for Rac in the control of the ERK pathway.

MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway

Cotransfection experiments demonstrated that p38 MAP kinase activation causes increased reporter gene expression mediated by the transcription factors ATF2 and Elk-1, demonstrating that the nucleus is one target of the p38MAP kinase signal transduction pathway.

Cloning of a Novel Mitogen-activated Protein Kinase Kinase Kinase, MEKK4, That Selectively Regulates the c-Jun Amino Terminal Kinase Pathway*

MEKK4 has a putative pleckstrin homology domain and a proline-rich motif, suggesting specific regulatory functions different from those of the previously characterized MEKKs.

Cloning and Characterization of MEK6, a Novel Member of the Mitogen-activated Protein Kinase Kinase Cascade (*)

MEK6 is a member of the p38 kinase cascade and efficiently phosphorylates p38 but not c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinases (ERK) family members in direct kinase assays.



Differential activation of ERK and JNK mitogen-activated protein kinases by Raf-1 and MEKK.

These results demonstrate the existence of two distinct Ras-dependent MAPK cascades--one initiated by Raf-1 leading to ERK activation, and the other initiated by MEKK leading to JNK activation.

The primary structure of MEK, a protein kinase that phosphorylates the ERK gene product.

The structure of this protein kinase, denoted MEK1, was elucidated from a complementary DNA sequence and shown to be a protein of 393 amino acids that is related most closely in size and sequence to the product encoded by the Schizosaccharomyces pombe byr1 gene.

Mitogen-activated protein (MAP) kinase phosphorylation of MAP kinase kinase: determination of phosphorylation sites by mass spectrometry and site-directed mutagenesis.

It is concluded that the phosphorylation of MKK at Thr292 and Thr386 does not interfere with catalysis in vitro and is likely to play a role in regulating the basal and stimulated MKK activities.

Activation of stress-activated protein kinase by MEKK1 phosphorylation of its activator SEK1

Induction of MEKK does not result in the activation of MAPK, but instead stimulates the stress-activated protein kinases (SAPKs)6–8 which are identical to a Jun amino-terminal kinase9,10 which in turn phosphorylates and activates SAPK.

Activation of MEK family kinases requires phosphorylation of two conserved Ser/Thr residues.

It is demonstrated that MEK is activated by phosphorylation of two adjacent serine/threonine residues and this activation mechanism is conserved in the MEK family kinases.

Role of SAPK/ERK kinase-1 in the stress-activated pathway regulating transcription factor c-Jun

A novel protein kinase, called SAPK/ERK kinase-1 (SEK1), which is structurally related to the MAP kinase kinases (MEKs) and is a potent activator of the SAPKs in vitro and in vivo is identified.

The stress-activated protein kinase subfamily of c-Jun kinases

The kinase p54s are the principal c-Jun N-terminal kinases activated by cellular stress and tumour necrosis factor (TNF)-α, hence they are designated stress-activated protein kinases, or SAPKs.