Protein kinase

A protein kinase is an enzyme that can transfer a [phosphate group]? from a donor molecule (usually ATP) to an amino acid residue of a protein. This mechanism is used in signal transduction for the regulation of enzymes; such a phosphorylation? can activate (or inhibit) the enzymatic activity of an enzyme. While most protein kinases are specialized on a single kind of amino acid residue, some of them have a dual kinase activity (they can phosphorylate two different kinds of amino acids). Protein kinases can be regulated by

• Activator proteins
• Inhibitor proteins
  • Pseudosubstrate?s
  • Autoinhibition (a part of the protein kinase mimics a pseudosubstrate)
• Ligands binding to regulatory subunits
• Cofactor?s / second messenger
• Phosphorylation in the active center (intrasterical regulation) by
  • other protein kinases (trans-phosphorylation)
  • itself (cis-phosphorylation/autophosphorylation)
• Localization in the cell

Serine?/threonine?-specific protein kinases

Serine/threonine protein kinases phosphorylate the OH group of serine or threonine (which have quite similar residues). These protein kinases can be regulated by:

• cAMP/cGMP
• Diacylglycerole
• Ca²⁺/calmodulin?

These kinases do not have a similar [consensus sequence]?; there is no common "target sequence" to be phosphorylated. As the substrate to be phosphorylated will align to the kinase by several key amino acids (usually by hydrophopic forces and [ion bond]?s), a kinase is usually spefic not to a single substrate, but to a whole "substrate family" with common properties. The kinases are usually inactivated by a pseudosubstrate? that binds to the kinase similar to a real substrate, but lacks the amino acid to phosphorylated. Its removal will activate the kinase.
The catalytic domain of the kinases is [highly conserved]?.

Phosphorylase kinase

Phosphorylase kinase was the first Ser/Thr? protein kinase to be discovered (in 1959 by Krebs et al.).

Protein kinase A

The protein kinase A consists of two domains, a small domain with several [β sheet]? structures, and a larger domain containing several [α helices]?. In the catalytic cleft between the domains (or lobes), the the substrate and ATP binding sites are located. On ATP and substrate binding, the two lobes rotate so the phosphate group of the ATP and the target amino acid of the substrate move into the right position for the catalytic reaction to take place.
Protein kinase A has several function within the cell, including regulation of glycogen?-, sugar- and lipid metabolism. It is controlled by cAMP; in the absence of cAMP, the kinase is a tetramer of each two regulatory and two catalytic subunits (R₂C₂), with the regulatory subints blocking the catalytic center of the catalytic subunits. Binding of cAMP to the regulatory subunit leads to the dissociation of active RC-dimers. Also, the catalytic subunit itself can be regulated by phosphorylation.

Protein kinase C

MAP kinases

Mos/Raf? kinases

Tyrosine-specific protein kinases

Histidine?-specific protein kinases

[Aspartic acid]?/[glutamic acid]?-specific protein kinases