MAPK signaling pathway

What is MAPK Signaling Pathway?

The mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration.

The Function of MAPK Signaling Pathway

The MAPK signaling pathway is essential in regulating many cellular processes including inflammation, cell stress response, cell differentiation, cell division, cell proliferation, metabolism, motility and apoptosis. The role of the MAPK pathway in cancer, immune disorders and neurodegenerative diseases has been well recognized.

The Processes of MAPK Signaling Pathway

Mammals express at least four distinctly regulated groups of MAPKs, extracellular signal-related kinases (ERK)-1/2, Jun amino-terminal kinases (JNK1/2/3), p38 proteins (p38alpha/beta/gamma/delta) and ERK5 that are activated by specific MAPKKs: MEK1/2 for ERK1/2, MKK3/6 for the p38, MKK4/7 (JNKK1/2) for the JNKs, and MEK5 for ERK5.

But each MAPKK can be activated by more than one MAPKKK, increasing the complexity and diversity of MAPK signaling. Presumably each MAPKKK confers responsiveness to distinct stimuli. As shown in the following picture, Classical mitogen-activated protein kinase (MAPK) pathway activation begins at the cell membrane where small GTPases and various protein kinases phosphorylate MAPKKKs. Subsequently, MAPKKKs directly phosphorylate and activate MAPKKs. Once phosphorylated, activated MAPKs phosphorylate numerous cytoplasmic substrates and ultimately modulate transcription factors that drive context-specific gene expression.

Although MAPK signaling cascades are depicted as simple linear, unidirectional groups of protein kinases, the pathway is highly complex, actually. A large degree of cross-talk within the MAPK cascades and other signaling networks exists. For example, interactions between mediators of the MAPK, PI3K networks, NFκB pathway and JAK-STAT pathway are well documented.

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