MAPKKMap Kinase Kinase
MAPKKMitogen-Activated Protein Kinase Kinase
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The MAPKKs in turn phosphorylate the most downstream group of effector serine/threonine kinases, that
The JNK pathway is activated by environmental stress (oxidative stress) and cytokines (tumor necrosis factor, TNF, and FAS) and involves a kinase cascade similar to the ERK pathway with a MAPKKK activating a MAPKK and the MAPKK subsequently phosphorylating JNK on critical threonine and tyrosine residues resulting in the activation of JNK; afterwards JNK translocate to the nucleus and regulate the activity of multiple transcription factors.
MAPK, mitogen-activated protein kinase; ERK, extracellular signal-related kinases; JNK, c-Jun N-terminal kinases; p38, p38 kinase; BMK1/ERK5, big MAP kinase 1; MAPKKK, MAP kinase kinase kinase; MAPKK, MAP kinase kinase; MAPK, MAP kinase; PLC, phospholipase C; IP3, inositol trisphosphate; DAG, diacylglycerol.
SHC-1 is an adaptor protein that connects MLK-1 and its downstream MAPKK MEK-1.
Incubation of RA SF with PD98059 or UO126, selective inhibitors of the MAPKK Mek1 (proximal activator of Erk), dramatically inhibited MMP-1 secretion in response to IL-1[beta] or TNF-[alpha].
These stimuli activate MAPKK kinases (MAPKKKs) via receptor dependent and independent mechanisms, followed by phosphorylation and activation of a downstream MAPK kinase (MAPKK) and then MAPKs.
2], whereas in Arabidopsis, AtMPK3 and AtMPK6, the orthologs of WIPK and SIPK, were activated by MAPKK kinase (MAPKKK), ANP1 (Kovtun et al.
On the basis of the observation that MAPKKK or NIK is required for the in vitro activation of IKK (33) and the identification of a canonical MAPKK activation loop motif (SxxxS) on both IKK[alpha] and IKK[beta] (34-38), researchers have speculated that NIK is a direct upstream kinase that can phosphorylate and activate IKK[alpha] and IKK[beta].
The activation of MAPKKs is regulated by other upstream serine-threonine kinases, called MAPKK kinases, which phosphorylate the MAPKKs on specific serine residues.