Phosphalidylinositol 4-phosphate 5-kinascs: A Novel Family

Richard A. Anderson, Joost C. Loiiens, Igor V. Boronenkov, Gregory J. Parker, Jeannette Kunz, Feng Lu

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Abstract

Phosphaüdylinositol 4,5-bisphosphate (PI4,5P2) is synthesized by P14P 5-kinases (PIP5K). PI4,5P2 is a precursor to second messengers and directly modulates cellular proteins and functions. The cDNAs encoding these kinases have been isolated, and their sequences demonstrate that the PIPSKs are distinct from known kinase families. The type I and type II PIP5K subfamilies share low homology, largely in the invariant residues, and may be functionally distinct enzyme families. The type I enzymes are stimulated by phosphatidic acid and small G-proteins, prime the Ca2-regulated secretory pathway, and the gene encoding type I|i is putatively defective in Friedreich's ataxia. The type II enzymes are distinguished by low activity toward PI4P and membranes, but their activity may be regulated by associations with receptors. Recently, we, in collaboration with the Majerus group, have discovered that the PIPSKs have an unanticipated specificity. These kinases will phosphorylate PI3P, a product of PI 3-kinases. Surprisingly, the product of P13P phosphorylation is PI3,4P2. Moreover, the kinases further phosphorylate PI3,4P2 to PI3,4,5P3 in a concerted reaction. These observations reveal a novel mechanism for synthesis of PI3,4P2 and PI3,4,5Pi. This switch in PIP5K. specificity is significant since PI4,5P2, PI3,4P2, and PI3,4,5P3 all have distinct biological activities. Substrate usage in vivo must be regulated, and this may occur by interactions with receptors, PI kinases. G-proteins, or phosphorylation by protein kinases.

Original languageEnglish
Pages (from-to)A1296
JournalFASEB Journal
Volume11
Issue number9
Publication statusPublished - Dec 1 1997

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ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Anderson, R. A., Loiiens, J. C., Boronenkov, I. V., Parker, G. J., Kunz, J., & Lu, F. (1997). Phosphalidylinositol 4-phosphate 5-kinascs: A Novel Family. FASEB Journal, 11(9), A1296.