Mitogen-activated protein kinase (MAPK) refers to a class of conserved serine/threonine kinase that being ubiquitously presented in eukaryotes. MAPK cascade pathway (MAPKKK-MAPKK-MAPK) is capable of transducing environmental signals through sequential phosphorylation, participating in regulating plant growth and development as well as a variety of biotic and abiotic stress signal transduction. MAPKs activation pathway plays a crucial role in the signal transduction process in eukaryotic cells. In 1982, during the study of the platelet-derived growth factor and epidermal growth factor, cooper found that a kind of intracellular protein (with relative molecular mass of 42 × 103) was subject to phosphorylation in its tyrosine residues. He then (in 1988) also found this protein in PMA-stimulated cells through two-dimensional electrophoresis.
At the same time, Ray had also successfully isolated a protein kinase of a molecular weight of 42X103 with its threonine and tyrosine residues being phosphorylated from the 3T3-L1 cells and named it MAPKs. Rossomando (1989) have clarified that this kind of protein that subjects to insulin-stimulated tyrosine / threonine residue phosphorylation is the same protein as the protein that subjects to tyrosine residue phosphorylation due to the stimulation of other growth factors and PMA; threonine / tyrosine residues double phosphorylation is a necessary condition for activation of this protein. Boulton (in 1990) had first cloned the cDNA encoding MAPKs; Crews (In 1993) had successfully identified the upstream kinase (MKKKs and MKKs) of MAPKs in mammalian cells by biochemical and molecular cloning techniques and defined a conservative three-kinase activation mode.
The composition of the MAPKs activation pathway
MAPKs activation pathway can be activated by a variety of factors including growth factors, cytokines, radiation, neurotransmitters, hormones and cell stress, etc. MAPKs activation pathway includes three sequentially activated protein kinase: MKKKs → MKKs → MAPKs. It has been found from mammalian cells of at least 14 kinds of MKKKs, 7 kinds of MKKs and 12 kinds of MAPKs.
(1) MKKKs: MKKKs is a kind of serine / threonine protein kinase. Specific MKKKs can be either activated through phosphorylation mediated by its MKKKs kinase (MKKKKs) or activated through the interaction with Ras or the small G protein in Rho family.
(2) MKKs: Gartner et al have confirmed, MKKs can recognize MAPKs to activate the threonine X tyrosine domain inside the ring, causing phosphorylation of the threonine and tyrosine residues and further being activated. Therefore, MKKs is a kind of protein kinase of dual specificity.
(3) MAPKs: MAPKs are a class of protein kinases that widely presented in the cytoplasm and are able to cause phosphorylation of serine/threonine in the inner substrate protein molecule. The kinase property of MAPKs is mediated by the proline, i.e., only being able to phosphorylate the proline-containing substrate protein in P1 region. The major targeting substrate of MAPKs is transcription factor, also includes a number of protein kinases, phospholipases and cytoskeletal associated proteins. Dual phosphorylation of serine and tyrosine residues is a necessary condition for the activation of MAPKs. Different MKKs are able to recognize the spatial structure of the threonine X tyrosine domain in specific MAPKs, instead of just recognizing the linear sequence in the activation domain.