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About MAPK / Mitogen-Activated Protein Kinase:
Mitogen-Activated Protein Kinase, also known as MAPK or MAP kinase, is a form of protein kinase, which is specific to two amino acids: serine and threonine. MAPKS can also be referred to as serine/threonine-specific kinases. MAPKS play an instrumental role in determining cellular responses to a broad spectrum of stimuli, regulating crucial cellular activities and functions.
MAPKS belong to a kinase group known as the CMGC, which comprises CDK//MAPK/GSK3/CLK.
MAPK Structure
The majority of MAPKS are structurally similar and they share characteristics, for example, a three-tiered pathway structure and shared substrate preferences. Most MAPKS are known as classical mitogen-activated protein kinases. However, there are a few that don’t share similar features or attributes, which are known as atypical MAPKS.
In their base form, MAP kinases are inactive, and they are required to go through a series of phosphorylation events to become active. These events take place in the activation loops found within the protein structure and are brought about by enzymes belonging to the STE protein kinase family.
In classical MAPKS, the activation loop contains a TxY sequence, which must be phosphorylated on both the tyrosine and threonine residues. In most cases, both in-vivo and in-vitro, tyrosine phosphorylation usually comes before threonine phosphorylation. This process is conducted by Ste7 protein kinase group members known as MAP2 kinases. MAP2 kinases can also be activated by MAP3 kinases (serine-threonine kinases) during the phosphorylation process, and this leads to the creation of MAPK pathways. These linear pathways are important because they deliver information from the cell membrane to the nucleus.
Mitogen-Activated Protein Kinase Mechanism
The creation of pathways is vital, as it facilitates the transmission of information from the outer reaches of the cell to the central nucleus. The MAPK/ERK pathway comprises a chain of proteins, which carry signals from the cell surface to the DNA found in the nucleus. The process begins when a signal molecule binds to the receptor and terminates when the DNA within the nucleus expresses a protein, which results in some form of cellular change. The chain goes through a series of processes, with MAPK and ERK proteins communicating with each other to add phosphate families through phosphorylation. The chain effectively acts as a series of on and off switches.
When the pathway doesn’t function properly, the chain can get stuck in either an ‘off’ or ‘on’ position. This is a phase identified in the development of cancerous cells.
MAPK Functions
Mitogen-activated protein kinases are involved in a diverse range of cellular functions, including: Cell proliferation, Gene expression, Cell development and survival, Apoptosis, Mitosis and Cell motility
MAP kinases are heavily involved in these processes due to their ability to communicate messages and signals from receptors on the outer surfaces of the cells to the DNA within the core cell nucleus.