protein kinase A

Examples of protein kinase A in the following topics:

• Signaling in Yeast

  • Budding yeasts are able to participate in a process that is similar to sexual reproduction that entails two haploid cells combining to form a diploid cell .
  • When mating factor binds to cell-surface receptors in other yeast cells that are nearby, they stop their normal growth cycles and initiate a cell signaling cascade that includes protein kinases and GTP-binding proteins that are similar to G-proteins.
  • Kinases are a major component of cellular communication.
  • Yeasts have 130 types of kinases.
  • Of the 130 kinase types in yeast, 97 belong to the 55 subfamilies of kinases that are found in other eukaryotic organisms.

• 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.
  • Phosphorylation adds a phosphate group to serine, threonine, and tyrosine residues in a protein, changing their shapes, and activating or inactivating the protein .
  • For example, phosphatases are enzymes that remove the phosphate group attached to proteins by kinases in a process called dephosphorylation.
  • In protein phosphorylation, a phosphate group is added to residues of the amino acids serine, threonine, and tyrosine.

• Plasma Membrane Hormone Receptors

  • When a hormone binds to its membrane receptor, a G protein that is associated with the receptor is activated.
  • The activated G protein in turn activates a membrane-bound enzyme called adenylyl cyclase.
  • Adenylyl cyclase catalyzes the conversion of ATP to cAMP. cAMP, in turn, activates a group of proteins called protein kinases, which transfer a phosphate group from ATP to a substrate molecule in a process called phosphorylation.
  • The binding of a hormone at a single receptor causes the activation of many G-proteins, which activates adenylyl cyclase.
  • Further amplification occurs as protein kinases, once activated by cAMP, can catalyze many reactions.

• Regulating Protein Activity and Longevity

  • The enzymes which are responsible for phosphorylation are known as protein kinases.
  • The addition of a phosphate group to a protein can result in either activation or deactivation; it is protein dependent.
  • The addition of an ubiquitin group to a protein marks that protein for degradation.
  • Ubiquitin acts like a flag indicating that the protein lifespan is complete.
  • One way to control gene expression is to alter the longevity of the protein: ubiquitination shortens a protein's lifespan.

• Two-Component Regulatory Systems

  • The KdpD sensor kinase proteins regulate the kdpFABC operon responsible for potassium transport in bacteria including E. coli and Clostridium acetobutylicum.
  • Here a hybrid HK autophosphorylates and then transfers the phosphoryl group to an internal receiver domain, rather than to a separate RR protein.
  • The kinase core has a unique fold, distinct from that of the Ser/Thr/Tyr kinase superfamily.
  • Most orthodox HKs, typified by the Escherichia coli EnvZ protein, function as periplasmic membrane receptors and have a signal peptide and transmembrane segment(s) that separate the protein into a periplasmic N-terminal sensing domain and a highly conserved cytoplasmic C-terminal kinase core.
  • This kinase is unusual in that it recognizes the tertiary structure of its target and is a member of a novel family unrelated to any previously described protein phosphorylating enzymes.

• Methods of Intracellular Signaling

  • One of the most common chemical modifications that occurs in signaling pathways is the addition of a phosphate group (PO4–3) to a molecule such as a protein in a process called phosphorylation .
  • The transfer of the phosphate is catalyzed by an enzyme called a kinase.
  • 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.
  • A-kinase is found in many different types of cells; the target proteins in each kind of cell are different.

• 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.
  • The genes that regulate the signaling proteins are one type of oncogene: a gene that has the potential to cause cancer.

• Regulator Molecules of the Cell Cycle

  • The levels of the four cyclin proteins fluctuate throughout the cell cycle in a predictable pattern .
  • Like all kinases, Cdks are enzymes (kinases) that phosphorylate other proteins.
  • Retinoblastoma proteins are a group of tumor-suppressor proteins common in many cells.
  • 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.

• Cytomegalovirus Infections

  • One viral protein blocks translocation of peptides into the lumen of the endoplasmic reticulum, while two other viral proteins cause degradation of MHC class I proteins before they reach the cell surface.
  • A vaccine against (CMV) is currently under investigation.
  • Its antiviral activity requires phosphorylation by the HCMV protein kinase, pUL97.
  • Finally, Foscarnet (FOS) has a different mode of action.
  • HCMV drugs have been designed to target the virus' DNA polymerase (pUL54), protein kinase (pUL97), and cellular kinases.

• Interferons

  • Both type I and type II IFNs activate a member of the CRK family of adaptor proteins called CRKL, a nuclear adaptor for STAT5 that also regulates signaling through the C3G/Rap1 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.