histidine kinase

(noun)

Histidine Kinases (HK) are multifunctional, typically transmembrane, proteins of the transferase class that play a role in signal transduction across the cellular membrane.

Related Terms

Examples of histidine kinase in the following topics:

  • Two-Component Regulatory Systems

    • Signal transduction occurs through the transfer of phosphoryl groups from adenosine triphosphate (ATP) to a specific histidine residue in the histidine kinases (HK).
    • Subsequently the histidine kinase catalyzes the transfer of the phosphate group on the phosphorylated histidine residues to an aspartic acid residue on the response regulator (RR).
    • Signal transducing histidine kinases are the key elements in two-component signal transduction systems.
    • Examples of histidine kinases are EnvZ, which plays a central role in osmoregulation, and CheA, which plays a central role in the chemotaxis system.
    • Histidine kinases usually have an N-terminal ligand-binding domain and a C-terminal kinase domain, but other domains may also be present.

  • Chemotaxis

    • The activation of the receptor by an external stimulus causes autophosphorylation in the histidine kinase, CheA, at a single highly-conserved histidine residue.
    • CheA in turn transfers phosphoryl groups to conserved aspartate residues in the response regulators CheB and CheY [note: CheA is a histidine kinase and it does not actively transfer the phosphoryl group.

  • Signaling in Yeast

    • Kinases are a major component of cellular communication.
    • Yeasts have 130 types of kinases.
    • More complex organisms such as nematode worms and fruit flies have 454 and 239 kinases, respectively.
    • Of the 130 kinase types in yeast, 97 belong to the 55 subfamilies of kinases that are found in other eukaryotic organisms.
    • The only obvious deficiency seen in yeasts is the complete absence of tyrosine kinases.

  • Termination of the Signal Cascade

    • Signal cascades convey signals to the cell through the phosphorylation of molecules by kinases.
    • A major component of cell signaling cascades is the phosphorylation of molecules by enzymes known as kinases.
    • For example, phosphatases are enzymes that remove the phosphate group attached to proteins by kinases in a process called dephosphorylation.

  • Biomolecules

    • It consists of a zinc ion coordinated by three imidazole nitrogen atoms from three histidine units.
    • The three coordinating histidine residues are shown in green, hydroxide in red and white, and the zinc in gray.

  • Methods of Intracellular Signaling

    • The transfer of the phosphate is catalyzed by an enzyme called a kinase.
    • Various kinases are named for the substrate they phosphorylate.
    • The main role of cAMP in cells is to bind to and activate an enzyme called cAMP-dependent kinase (A-kinase).
    • A-kinase regulates many vital metabolic pathways.
    • Enzymes known as kinases phosphorylate PI to form PI-phosphate (PIP) and PI-bisphosphate (PIP2).

  • Cell Signaling and Cell Growth

    • Most growth factors bind to cell-surface receptors that are linked to tyrosine kinases.
    • These cell-surface receptors are called receptor tyrosine kinases (RTKs).
    • Activation of RTKs initiates a signaling pathway that includes a G-protein called RAS, which activates the MAP kinase pathway described earlier.
    • The enzyme MAP kinase then stimulates the expression of proteins that interact with other cellular components to initiate cell division.

  • Interferons

    • STAT activation initiates the most well-defined cell signaling pathway for all IFNs, the classical Janus kinase-STAT (JAK-STAT) signaling pathway.
    • Type I IFNs further activate p38 mitogen-activated protein kinase (MAP kinase) to induce gene transcription.
    • Antiviral and antiproliferative effects specific to type I IFNs result from p38 MAP kinase signaling.
    • The phosphatidylinositol 3-kinase (PI3K) signaling pathway is also regulated by both type I and type II IFNs.
    • PI3K activates P70-S6 Kinase 1, an enzyme that increases protein synthesis and cell proliferation; phosphorylates of ribosomal protein s6, which is involved in protein synthesis; and phosphorylates a translational repressor protein called eukaryotic translation-initiation factor 4E-binding protein 1 (EIF4EBP1) in order to deactivate it.

  • Regulator Molecules of the Cell Cycle

    • Two groups of proteins, called cyclins and cyclin-dependent kinases (Cdks), are responsible for the progress of the cell through the various checkpoints.
    • Like all kinases, Cdks are enzymes (kinases) that phosphorylate other proteins.
    • Cyclin-dependent kinases (Cdks) are protein kinases that, when fully activated, can phosphorylate and activate other proteins that advance the cell cycle past a checkpoint.
    • To become fully activated, a Cdk must bind to a cyclin protein and then be phosphorylated by another kinase.

  • Control of Catabolic Pathways

    • The last step in glycolysis is catalyzed by pyruvate kinase.
    • (Recall that fructose-1,6-bisphosphate is an intermediate in the first half of glycolysis. ) The regulation of pyruvate kinase involves phosphorylation, resulting in a less-active enzyme.
    • Pyruvate kinase is also regulated by ATP (a negative allosteric effect).
    • Pyruvate dehydrogenase is also regulated by phosphorylation: a kinase phosphorylates it to form an inactive enzyme, and a phosphatase reactivates it.
    • The kinase and the phosphatase are also regulated.