Mitogen-activated protein kinase

ERK2-phosphorylated

Raf-activation-cycle-sketch

MAPK-pathway-mammalian

MAPK-pathway-yeast

MAPK-evolutionary-tree

D-motif-overview

Mitogen-activated protein kinase (MAPK) is a type of protein kinase that is specific to the amino acids serine, threonine, and tyrosine. MAPKs are involved in directing cellular responses to a diverse array of stimuli, such as mitogens, osmotic stress, heat shock, and proinflammatory cytokines. They regulate various cellular activities, including gene expression, mitosis, differentiation, proliferation, and cell survival/apoptosis.

Function

MAPKs are integral to the signal transduction pathways that convey extracellular signals to the intracellular machinery. They are activated through a cascade of phosphorylation events, typically involving a three-tiered kinase module: a MAPK kinase kinase (MAPKKK), a MAPK kinase (MAPKK), and the MAPK itself. This cascade ensures the amplification and specificity of the signal.

Types of MAPKs

There are several types of MAPKs, each with distinct functions and activation mechanisms:

• ERK1/2 (Extracellular signal-regulated kinases)
• JNK (c-Jun N-terminal kinases)
• p38 MAPK
• ERK5 (also known as BMK1)

Activation Mechanism

The activation of MAPKs involves a series of phosphorylation events. Typically, a MAPKKK phosphorylates and activates a MAPKK, which in turn phosphorylates and activates the MAPK. This phosphorylation usually occurs on specific threonine and tyrosine residues within the activation loop of the MAPK.

Biological Roles

MAPKs play crucial roles in various cellular processes:

• Cell Growth and Proliferation: ERK1/2 pathways are often associated with cell growth and proliferation.
• Stress Response: JNK and p38 MAPKs are typically activated in response to stress stimuli and are involved in the regulation of apoptosis.
• Differentiation: MAPKs are involved in the differentiation of various cell types.
• Inflammation: p38 MAPK is particularly important in the inflammatory response.

Clinical Significance

Dysregulation of MAPK pathways is implicated in various diseases, including cancer, diabetes, and neurodegenerative diseases. Targeting MAPK pathways is a therapeutic strategy in the treatment of these conditions.

Related Pages

• Protein kinase
• Signal transduction
• Gene expression
• Apoptosis
• Cell proliferation
• ERK1/2
• JNK
• p38 MAPK
• ERK5

See Also

• Kinase
• Phosphorylation
• Cell signaling
• Mitogen