phosphorylation

Examples of phosphorylation in the following topics:

• 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 .
  • In protein phosphorylation, a phosphate group is added to residues of the amino acids serine, threonine, and tyrosine.

• Methods of Intracellular Signaling

  • Various kinases are named for the substrate they phosphorylate.
  • Phosphorylation of serine and threonine residues often activates enzymes.
  • Phosphorylation may activate or inactivate enzymes; the reversal of phosphorylation, dephosphorylation by a phosphatase, will reverse the effect.
  • It phosphorylates serine and threonine residues of its target proteins, activating them in the process.
  • Enzymes known as kinases phosphorylate PI to form PI-phosphate (PIP) and PI-bisphosphate (PIP2).

• The Energy-Requiring Steps of Glycolysis

  • The first step in glycolysis is catalyzed by hexokinase, an enzyme with broad specificity that catalyzes the phosphorylation of six-carbon sugars.
  • Hexokinase phosphorylates glucose using ATP as the source of the phosphate, producing glucose-6-phosphate, a more reactive form of glucose.
  • This reaction prevents the phosphorylated glucose molecule from continuing to interact with the GLUT proteins.
  • The third step is the phosphorylation of fructose-6-phosphate, catalyzed by the enzyme phosphofructokinase.
  • The first half of glycolysis uses two ATP molecules in the phosphorylation of glucose, which is then split into two three-carbon molecules.

• Chemiosmosis and Oxidative Phosphorylation

  • The production of ATP using the process of chemiosmosis in mitochondria is called oxidative phosphorylation.
  • In oxidative phosphorylation, the hydrogen ion gradient formed by the electron transport chain is used by ATP synthase to form ATP.

• ATP in Metabolism

  • Phosphorylation by ATP alters the structure of the integral protein that functions as the pump, changing its affinity for sodium and potassium.
  • Sometimes phosphorylation of an enzyme leads to its inhibition.
  • For example, the pyruvate dehydrogenase (PDH) complex could be phosphorylated by pyruvate dehydrogenase kinase (PDHK).
  • Phosphorylation refers to the addition of the phosphate (~P).
  • In phosphorylation reactions, the gamma phosphate of ATP is attached to a protein.

• Regulator Molecules of the Cell Cycle

  • To be fully active, the Cdk/cyclin complex must also be phosphorylated in specific locations.
  • Like all kinases, Cdks are enzymes (kinases) that phosphorylate other proteins.
  • Phosphorylation activates the protein by changing its shape.
  • The proteins phosphorylated by Cdks are involved in advancing the cell to the next phase. .
  • As the cell increases in size, Rb is slowly phosphorylated until it becomes inactivated.

• The Energy-Releasing Steps of Glycolysis

  • The sugar is then phosphorylated by the addition of a second phosphate group, producing 1,3-bisphosphoglycerate.
  • (This is an example of substrate-level phosphorylation. ) A carbonyl group on the 1,3-bisphosphoglycerate is oxidized to a carboxyl group, and 3-phosphoglycerate is formed.
  • The last step in glycolysis is catalyzed by the enzyme pyruvate kinase (the enzyme in this case is named for the reverse reaction of pyruvate's conversion into PEP) and results in the production of a second ATP molecule by substrate-level phosphorylation and the compound pyruvic acid (or its salt form, pyruvate).
  • The second half of glycolysis involves phosphorylation without ATP investment (step 6) and produces two NADH and four ATP molecules per glucose.

• ATP: Adenosine Triphosphate

  • When ATP is hydrolyzed, it transfers its gamma phosphate to the pump protein in a process called phosphorylation.
  • By donating free energy to the Na+/K+ pump, phosphorylation drives the endergonic reaction.
  • ATP is required for the phosphorylation of glucose, creating a high-energy but unstable intermediate.
  • This phosphorylation reaction causes a conformational change that allows enzymes to convert the phosphorylated glucose molecule to the phosphorylated sugar fructose.

• Regulating Protein Activity and Longevity

  • Because proteins are involved in every stage of gene regulation, the phosphorylation of a protein (depending on the protein that is modified) can alter accessibility to the chromosome, can alter translation (by altering transcription factor binding or function), can change nuclear shuttling (by influencing modifications to the nuclear pore complex), can alter RNA stability (by binding or not binding to the RNA to regulate its stability), can modify translation (increase or decrease), or can change post-translational modifications (add or remove phosphates or other chemical modifications).
  • All of these protein activities are affected by the phosphorylation process.
  • The enzymes which are responsible for phosphorylation are known as protein kinases.

• Cancer and Transcriptional Control

  • Mutations that activate transcription factors, such as increased phosphorylation, can increase the binding of a transcription factor to its binding site in a promoter.
  • This can lead to increased phosphorylation of key transcription factors that increase transcription.