BLOCK-iT™ RNAi Express

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MAP Kinase Pathway

Mitogen-activated protein kinases (MAPK) are a family of serine/threonine kinases that respond to diverse stimuli within a tiered phosphorelay system (Figure 1). MAPK activation can occur in response to growth factors, differentiation agents, hormones, cytokines, and environmental stress. Pathway specificity is achieved through the integration of distinct signaling modules comprised of specific MAPK subfamilies including: extracellular signal regulated kinase (ERK1/2), c-Jun N-terminal kinase (JNK1/2/3), p38 proteins (p38α,β,γ,δ), and Big MAPK (BMK/ERK5). Each of these MAPK subtype containing modules consists of a three tier regulatory cascade of MAPKKKs, MAPKKs, and MAPKs. MAPKKKs phosphorylate MAPKKs on serine and threonine residues in response to cellular activation, often through direct interaction with small GTPases or kinases (MAPKKKKs). These dual specificity MAPKKs (also known as MEKs or MKKs) phosphorylate specific MAPKs on conserved Thr and Tyr residues. Following activation, MAPKs catalyze the phosphorylation of other protein kinases, phospholipases, transcription factors, and cytoskeletal proteins leading to changes in gene transcription, protein synthesis, metabolism, cell survival, cell proliferation, and cell motility.

MAP Kinase Pathway Validated Stealth RNAi™ siRNA

MAPK

MAPKK

MAPKKK

Upstream Regulators of MAPK

Scaffolding Proteins

Targets of MAPK

Figure 1. Organization of MAP Kinase Signal Transduction Cascade

References

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