Serine/threonine-protein kinase

Identifiers
EC number	2.7.11.1
CAS number	9032-55-9
Alt. names
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway

Overview

Serine/threonine-protein kinases are a group of enzymes that specifically phosphorylate the hydroxyl group of serine or threonine residues in proteins. This post-translational modification is a critical regulatory mechanism in cell signaling pathways, affecting various cellular processes such as cell cycle, apoptosis, and metabolism.

Structure

Serine/threonine-protein kinases typically have a conserved catalytic core that is responsible for their enzymatic activity. This core consists of approximately 250-300 amino acids and is divided into several subdomains that are involved in ATP binding and substrate recognition. The structure of these kinases often includes a small N-terminal lobe and a larger C-terminal lobe, with the active site located in a cleft between these lobes.

Function

The primary function of serine/threonine-protein kinases is to transfer a phosphate group from ATP to the hydroxyl group of serine or threonine residues on target proteins. This phosphorylation event can alter the activity, localization, or interaction of the substrate protein, thereby modulating various signaling pathways. These kinases play crucial roles in regulating the cell cycle, growth, differentiation, and apoptosis.

Classification

Serine/threonine-protein kinases are classified into several families based on sequence similarity and functional characteristics. Some of the major families include:

• Protein kinase A (PKA): Involved in the regulation of glycogen, sugar, and lipid metabolism.
• Protein kinase C (PKC): Plays a role in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and threonine amino acid residues.
• Mitogen-activated protein kinase (MAPK): Involved in directing cellular responses to a diverse array of stimuli, such as mitogens, osmotic stress, heat shock, and proinflammatory cytokines.
• Cyclin-dependent kinase (CDK): Essential for the control of the cell cycle.

Mechanism of Action

The mechanism of action of serine/threonine-protein kinases involves the binding of ATP and the substrate protein to the active site of the enzyme. The gamma phosphate of ATP is then transferred to the hydroxyl group of the serine or threonine residue on the substrate. This reaction is facilitated by the presence of divalent metal ions, such as magnesium or manganese, which are required for kinase activity.

Regulation

The activity of serine/threonine-protein kinases is tightly regulated by various mechanisms, including:

• Phosphorylation: Kinases can be activated or inactivated by phosphorylation at specific sites.
• Protein-protein interactions: Binding of regulatory subunits or interacting proteins can modulate kinase activity.
• Localization: The subcellular localization of kinases can affect their access to substrates and regulators.
• Proteolytic cleavage: Some kinases are activated by proteolytic cleavage.

Clinical Significance

Dysregulation of serine/threonine-protein kinases is implicated in numerous diseases, including cancer, diabetes, and neurodegenerative disorders. For example, mutations in the BRAF gene, which encodes a serine/threonine-protein kinase, are associated with various types of cancer, including melanoma. As a result, these kinases are important targets for therapeutic intervention, and several kinase inhibitors have been developed for clinical use.

See Also

• Tyrosine kinase
• Phosphorylation
• Signal transduction

External Links

• UniProt Database
• Protein Data Bank