Phosphatidylinositol phosphate kinases

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Phosphatidylinositol phosphate kinases (PIPK) are kinases that phosphorylate the phosphoinositides PtdInsP and PtdInsP2 that are derivatives of phosphatidylinositol (PtdIns). It has been found that PtdIns is only phosphorylated on three (3,4,5) of its five hydroxyl groups, possibly because D-2 and D-6 hydroxyl groups cannot be phosphorylated because of steric hindrance. [1] All 7 combinations of phosphorylated PtdIns have been found in animals, all except PtdIns(3,4,5)P3 have been found in plants. [2]

PIPKs are today divided into three groups, type I, II and III that share significant sequence homology but differ in the substrate specificities, subcellular localisations and functions. [3] Type 1 are PIPKs that phosphorylate PtdIns4P to PtdIns(4,5)P2 and are called PtdIns4P 5-kinases because they phosphorylate on the D-5 hydroxyl group. Type II PIPKs phosphorylate PtdIns5P at the D-4 site and are called PtdIns5P 4-kinases. And finally PIPKs of type III are PtdIns3P 5-kinases that phosphorylate PtdIns to PtdIns(3,5)P2, which prototype is Fab1 in yeast (see for descriptive picture). The substrate specificity of type I and II depends on the so-called activation loop. The activation loop is a segment of 22 to 27 amino acid residues, located close to the C-terminal end of the catalytic domain in all PIPKs.[ citation needed ] When the activation loops of a type I and a type II PIPK were swapped, the chimera with type I backbone showed specificity for type II substrate, and vice versa for the other chimera. [4]

List of PIPKs

Related Research Articles

Inositol trisphosphate or inositol 1,4,5-trisphosphate abbreviated InsP3 or Ins3P or IP3 is an inositol phosphate signaling molecule. It is made by hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), a phospholipid that is located in the plasma membrane, by phospholipase C (PLC). Together with diacylglycerol (DAG), IP3 is a second messenger molecule used in signal transduction in biological cells. While DAG stays inside the membrane, IP3 is soluble and diffuses through the cell, where it binds to its receptor, which is a calcium channel located in the endoplasmic reticulum. When IP3 binds its receptor, calcium is released into the cytosol, thereby activating various calcium regulated intracellular signals.

Phosphatidylinositol Chemical compound

Phosphatidylinositol consists of a family of lipids as illustrated on the right, where red is x, blue is y, and black is z, in the context of independent variation, a class of the phosphatidylglycerides. In such molecules the isomer of the inositol group is assumed to be the myo- conformer unless otherwise stated. Typically phosphatidylinositols form a minor component on the cytosolic side of eukaryotic cell membranes. The phosphate group gives the molecules a negative charge at physiological pH.

Phosphoinositide phospholipase C

Phosphoinositide phospholipase C (PLC) is a family of eukaryotic intracellular enzymes that play an important role in signal transduction processes. These enzymes belong to a larger superfamily of Phospholipase C. Other families of phospholipase C enzymes have been identified in bacteria and trypanosomes. Phospholipases C are phosphodiesterases.

Phosphatidylinositol (3,4,5)-trisphosphate Chemical compound

Phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3), abbreviated PIP3, is the product of the class I phosphoinositide 3-kinases (PI 3-kinases) phosphorylation of phosphatidylinositol (4,5)-bisphosphate (PIP2). It is a phospholipid that resides on the plasma membrane.

Phosphoinositide 3-kinase

Phosphoinositide 3-kinases (PI3Ks), also called phosphatidylinositol 3-kinases, are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer.

Class III PI 3-kinase is a subgroup of the enzyme family, phosphoinositide 3-kinase that share a common protein domain structure, substrate specificity and method of activation.

Phosphatidylinositol 4,5-bisphosphate Chemical compound

Phosphatidylinositol 4,5-bisphosphate or PtdIns(4,5)P2, also known simply as PIP2 or PI(4,5)P2, is a minor phospholipid component of cell membranes. PtdIns(4,5)P2 is enriched at the plasma membrane where it is a substrate for a number of important signaling proteins.

Phosphatidylinositol 3-phosphate Chemical compound

Phosphatidylinositol 3-phosphate (PtdIns3P) is a phospholipid found in cell membranes that helps to recruit a range of proteins, many of which are involved in protein trafficking, to the membranes. It is the product of both the class II and III phosphoinositide 3-kinases activity on phosphatidylinositol.

Phosphatidylinositol 3,4-bisphosphate

Phosphatidylinositol (3,4)-bisphosphate is a minor phospholipid component of cell membranes, yet an important second messenger. The generation of PtdIns(3,4)P2 at the plasma membrane activates a number of important cell signaling pathways.

Pleckstrin homology domain

Pleckstrin homology domain or (PHIP) is a protein domain of approximately 120 amino acids that occurs in a wide range of proteins involved in intracellular signaling or as constituents of the cytoskeleton.

Phosphatidylinositol 3,5-bisphosphate is one of the seven phosphoinositides found in eukaryotic cell membranes. In quiescent cells, the PtdIns(3,5)P2 levels, typically quantified by HPLC, are the lowest amongst the constitutively present phosphoinositides. They are approximately 3 to 5-fold lower as compared to PtdIns3P and PtdIns5P levels, and more than 100-fold lower than the abundant PtdIns4P and PtdIns(4,5)P2. PtdIns(3,5)P2 was first reported to occur in mouse fibroblasts and budding yeast S. cerevisiae in 1997. In S. cerevisiae PtdIns(3,5)P2 levels increase dramatically during hyperosmotic shock. The response to hyperosmotic challenge is not conserved in most tested mammalian cells except for differentiated 3T3L1 adipocytes.

1-phosphatidylinositol 4-kinase

In enzymology, a 1-phosphatidylinositol 4-kinase is an enzyme that catalyzes the chemical reaction

In enzymology, a phosphatidylinositol-4-phosphate 3-kinase is an enzyme that catalyzes the chemical reaction

PIP4K2A Kinase enzyme

Phosphatidylinositol-5-phosphate 4-kinase type-2 alpha is an enzyme that in humans is encoded by the PIP4K2A gene.

PIP4K2B

Phosphatidylinositol-5-phosphate 4-kinase type-2 beta is an enzyme that in humans is encoded by the PIP4K2B gene.

Bisphosphate may refer to:

Phosphatidylinositol 5-phosphate (PtdIns5P) is a phosphoinositide, one of the phosphorylated derivatives of phosphatidylinositol (PtdIns), that are well-established membrane-anchored regulatory molecules. Phosphoinositides participate in signaling events that control cytoskeletal dynamics, intracellular membrane trafficking, cell proliferation and many other cellular functions. Generally, phosphoinositides transduce signals by recruiting specific phosphoinositide-binding proteins to intracellular membranes.

Lewis C. Cantley is an American cell biologist and biochemist who has made significant advances to the understanding of cancer metabolism. Among his most notable contributions are the discovery and study of the enzyme PI-3-kinase, now known to be important to understanding cancer and diabetes mellitus. He is currently Meyer Director and Professor of Cancer Biology at the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine in New York City. He was formerly a professor in the Departments of Systems Biology and Medicine at Harvard Medical School, and the Director of Cancer Research at the Beth Israel Deaconess Medical Center, in Boston, Massachusetts. In 2016, he was elected Chairman of the Board for the Hope Funds for Cancer Research.

Leonard (Len) R Stephens FRS is a molecular biologist, senior group leader and associate director at the Babraham Institute.

Phillip (Phill) Thomas Hawkins FRS is a molecular biologist, senior group leader at the Babraham Institute.

References

  1. Pettitt TR, Dove SK, Lubben A, Calaminus SDJ, Wakelam MJO. Analysis of intact phosphoinositides in biological samples. American Soc f Biochem and Mol Biol 2006; 47:1588-1596
  2. Muller-Roeber B, Pical C. Inositol Phospholipid Metabolism in Arabidopsis. Characterized and Putative Isoforms of Inositol Phospholipid Kinase and Phosphoinositide-Specific Phospholipase C. Plant Physiol 2002 130:22–46
  3. Anderson RA, Boronenkov IV, Doughman SD, Kunz J, Loijens JC . Phosphatidylinositol phosphate kinases, a multifaceted family of signalling enzymes. J Biol Chem 1999; 274:9907-9910
  4. Kunz J, Wilson MP, Kisseleva M, Hurley JH, Majerus PW, Anderson RA. The activation loop of phosphatidylinositol phosphate kinases determines signaling specificity. Mol Cell 2000 5:1-11