Mitogen-activated protein kinase (MAPK) interacting kinase (MKN) is turned on by the oncogenic MAPK (ERK) signaling pathway. They phosphorylate eukaryotic initiation factor (eIF) 4E, a protein that recruits ribosomes to mRNA and mediates its translation. Importantly, overexpression of eIF4E can transform cells and its function is controlled by a second oncogenic pathway (the mechanism target of rapamycin complex 1).

MAPK (ERK) signaling pathway

The MAPK/ERK pathway (also known as the Ras-Raf-MEK-ERK pathway) is a protein chain in the cell that transmits signals from cell surface receptors to DNA in the nucleus. The signal begins when the signal molecule binds to a receptor on the cell surface; the signal ends when the DNA in the nucleus expresses a protein and causes certain changes in the cell (such as cell division). This pathway includes many proteins, including MAPK (mitogen-activated protein kinase, originally called ERK, extracellular signal-regulated kinase), which communicates by adding phosphate groups (phosphorylation) to neighboring proteins, this protein acts as an "on" or "on" switch. When a protein in the pathway is mutated, it may get stuck in the "on" or "off" position, a necessary step in the development of many cancers. MAPK/Components of the ERK pathway are found in cancer cells. Drugs that can reverse the "on" or "off" switch are being studied as a cancer treatment.

Introductions

MAPK interacting protein kinase 1 (MAPn) interacting kinase 1 (MKN) was discovered during the study of bacterial classic MAPKs regulatory protein expression libraries. MKN1 regulates phosphorylation of multiple substrates, such as eukaryotic translation initiation factor (eIF4E) and sprouty2. sprouty2 can inhibit the Ras/ERK signaling pathway by binding to growth factor receptor bound protein 2 (GRB2). Other researchers have found that eIF4E can exert anti-apoptotic effects by promoting Bcl-2 expression. Both sprouty2 and eIF4E can be phosphorylated by MKN and regulated by MKN. MKN phosphorylates sprouty2 can protect the stability of sprouty2 and prevent it from binding to c-Cbl to cause degradation. MKN phosphorylates eIF4E through this pathway to promote the formation of the eIF4F translation initiation complex, and promote the recruitment of certain mRNAs such as TNF-α in the ribosome. Recent studies have shown that MKN is closely related to the occurrence and development of various tumors.

MAPK

MAPK is an important transmitter of signal transmission from the cell surface to the interior of the nucleus. Mitogen-activated protein kinase (MAPK) is a group of serine-threonine that can be activated by different extracellular stimuli such as cytokines, neurotransmitters, hormones, cell stress and cell adhesion. Protein kinase. MAPK is named because cultured cells are identified when activated by mitogens such as growth factors. All eukaryotic cells can express MAPK. The basic composition of the MAPK pathway is a three-level kinase model that is conserved from yeast to humans, including MAPK kinase kinase (MKKK), MAP kinase kinase (MKK), and MAPK. These three kinases can Activation in turn regulates many important cell physiological/pathological processes such as cell growth, differentiation, environmental stress adaptation, and inflammatory response. The mitogen-activated protein kinases (MAP kinases, MAPK) chain is one of the important pathways in eukaryotic signaling networks, and plays a key role in gene expression regulation and cytoplasmic functional activities. The MAPK chain consists of three types of protein kinases, MAP3K-MAP2K-MAPK, and transmits upstream signals to downstream response molecules through sequential phosphorylation. MAPK belongs to the CMGC (CDK/MAPK/GSK3/CLK) kinase group. The closest proteins related to MAPKs are cyclin-dependent kinases (CDKs).

Figure 1. Protein structure of MAPK.

MAPK pathway

The MAPK pathway is one of the common crossover pathways of cell proliferation, stress, inflammation, differentiation, functional synchronization, transformation, and apoptosis. It transmits extracellular signals through receptors, G protein/small G, protein kinase, A signal network composed of transcription factors is transmitted to the cell and participates in cell proliferation, differentiation, canceration, metastasis, apoptosis, etc. Different growth stimuli and stress stimuli are in different cells. Different signaling pathways confined by different cytoskeletons can produce multiple effects. MAPK activation is the final step in the intracellular phosphorylation cascade. The classic MAPK cascade includes MAPKKKK (such as Ras, Rho)-MAPKK kinase (MAPKKK)-MAPKK serine/threonine phosphorylation-activated MAPKK will MAPK threonine/tyrosine double phosphorylation activates MAPK. Enhancers in the MAPK signal transduction pathway can be combined with MAPKKKs, MAPKKs and MAPKs, increasing their ability to activate them by upstream kinases.

Reference:

1. Xie, J; et al. The MAP kinase-interacting kinases (MNKs) as targets in oncology. Expert Opinion on Therapeutic Targets. 2019