Biology Reference
In-Depth Information
Protein kinases catalyze the transfer of a phosphate group fromATP onto
an amino acid of a substrate protein with a free hydroxyl group, namely, ser-
ine, threonine, and tyrosine ( Fig. 6.1A ). As such, protein kinases are classi-
cally divided into the families of serine/threonine kinases, tyrosine kinases,
and dual-specificity kinases. 8 Protein kinases are further divided into either
receptor or nonreceptor kinases, depending on whether they are localized at
the surface of cells and play a role in integrating extracellular cues to be fed
into the cell. The human genome is estimated to harbor 514 genes encoding
protein kinases, known as the kinome, which corresponds to 2% of all eu-
karyotic genes. 9 Protein kinases are central to the regulation of most cellular
processes, throughout development and cell differentiation, metabolism,
gene transcription, cell growth and division, DNA replication, protein deg-
radation, apoptosis, and immune response. 10,11 They play a major role in
C
A
ATP
ADP
kinase
OH (Ser/Thr/Tyr)
P
substrate
substrate
cAMP-dependent
kinase
Cyclin-dependent
kinase
B
P
Protein/protein
interaction
P
Nucleus
Localization
Activity
Conformation
P
P
Proteolysis
Figure 6.1 Protein kinase: structure, function, and mechanisms of action. (A) A protein
kinase is an enzyme that catalyzes the transfer of a phosphate group from ATP to a
substrate protein, a process known as phosphorylation. This reaction consists in the
removal of a phosphate group from ATP, followed by its covalent attachment to amino
acids with a free hydroxyl group, namely, serine, threonine, and tyrosine. (B) Phosphor-
ylation usually results in a functional change of the target protein (substrate) by
changing enzyme activity, conformation, subcellular localization, or association with
partners. (C) Structural fold of two protein kinases—cAMP-dependent kinase (PDB struc-
ture 2CPK) and cyclin-dependent kinase 2 (PDB structure 1B38).
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