• 2018-07
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • In different body organs a number of


    In different body organs, a number of biological functions are generally mediated by binding of the extracellular substances to the particular transmembrane receptors, which results in subsequent signal stimulation by intracellular signaling cascades. These cascades function over the complex networks of interacting proteins that link the specific signals to a wide range of intracellular targets and lead to the modulation of the processes of transcription, transduction, translation, proliferation, differentiation and cell death. However, the processes are much more complicated within each cell, where different enzymes are perfectly regulated and perform their functions on multiple substrates. Interesting advances have been made to explore the functions of intracellular processes, still our knowledge of such cascades is narrow. The mitogen-activated protein kinase (MAPK) cascades are found as the central blocks of the structure of the intracellular signaling networks (Bogoyevitch and Court, 2004; Kuida and Boucher, 2004). MAPKs are a family of serine/threonine (Ser/Ter) protein kinases with important roles in various essential functions of cholesterol absorption inhibitor including differentiation, proliferation, survival, motility and stress response. The main subgroups of MAPKs are the extracellular signal-regulated kinase (ERK)1 and 2, c-Jun N-terminal kinases (JNK) 1–3, and p38 isoforms (p38α, β, γ, and δ), however the number of MAPK cascade is currently growing, since novel MAPKs are identified constituently and are not indicated to any recognized pathway (Arthur and Ley, 2013; Avruch, 2007). Small G proteins are responsible for initiation of signals transmission in such pathways, which in return stimulate a series of cytoplasmic protein kinases and nuclear targets. Partial purification of the cytoplasmic proteins (50−60 kDa) can regulate the phosphorylation of the MAPKs on both threonine and tyrosine residues in association with an enhanced MAPK catalytic function (Bogoyevitch and Court, 2004; Kuida and Boucher, 2004). In general, each cascade is consist of three to five tiers including MAPK kinase kinase (MAPKK), MAP3K, MAP4K, MAPK and MAPKAPK, as well as three tiers out of them (MAP3K, MAPKK, and MAPK), as the main cascades. In short, the MAPKKK causes the activation and phosphorylation of the downstream MAPK/ERK kinase (MEK), resulting in phosphorylation associated enhancement of MAPK function. Activation of a kinase component in each tier, phosphorylates proteins in the next tier, finally the downstream agent phosphorylates the target regulatory substances and modulates the specific biological effect within the cell. All of MAPK family members are participating in signals transition from different ligands, determining the cell\'s fate due to the specific extracellular stimulations (Arthur and Ley, 2013; Kuida and Boucher, 2004). Among the main mammalian MAPK cascades, ERK/MAPK pathway is generally involved in cell survival; however, p38/MAPK, SAPK and JNK pathways are mostly accompanied with apoptosis (Anderson and Tolkovsky, 1999; O\'Sullivan et al., 2009). It has been found that several stimuli are responsible for the induction of MAPKs, although JNK and p38 kinase are mainly activated by stress stimuli including ionizing radiation and cytokines, additionally the activation of ERK is in respond to the phorbol esters and growth factors (Roux and Blenis, 2004). ERK is the first cascade of MAPK that has been elucidated (Seger and Krebs, 1995). The signal transduction pathways of all the subgroups of MAPKs have been widely studies, typically for their involvements in pathological events of cancer investigations. ERK/MAPK has a key role in cell survival, mediated by cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) and mammalian target of rapamycin (mTOR). Induction of CREB is a crucial contributor of transcription of the genes that are involved in cell survival, also mTOR associates with cascades of cell survival through translational (Cao et al., 2010). According to the type of stimulus, ERK also has been reported to be implicated with cell death through mechanisms involving apoptosis (by activation of caspase-8, stimulation of cytochrome c release via modulation of Bcl-2 family protein, upregulation of p53 and Cytosolic phospholipase A2); and the type II programmed cell death (stimulation of LC3-I/LC3-II, beclin 1, BNIP-3, G-interacting protein and cysteine–cathepsin B) (Cagnol and Chambard, 2010).