Chapter

Phosphoinositides II: The Diverse Biological Functions

Volume 59 of the series Subcellular Biochemistry pp 389-412

Date:

Defining Signal Transduction by Inositol Phosphates

  • Stephen B. ShearsAffiliated withInositol Signaling Section, Laboratory of Signal Transduction, NIEHS, NIH, DHHS, Research Triangle Park Email author 
  • , Sindura B. GanapathiAffiliated withInositol Signaling Section, Laboratory of Signal Transduction, NIEHS, NIH, DHHS, Research Triangle Park
  • , Nikhil A. GokhaleAffiliated withInositol Signaling Section, Laboratory of Signal Transduction, NIEHS, NIH, DHHS, Research Triangle Park
  • , Tobias M. H. SchenkAffiliated withInositol Signaling Section, Laboratory of Signal Transduction, NIEHS, NIH, DHHS, Research Triangle Park
  • , Huanchen WangAffiliated withInositol Signaling Section, Laboratory of Signal Transduction, NIEHS, NIH, DHHS, Research Triangle Park
  • , Jeremy D. WeaverAffiliated withInositol Signaling Section, Laboratory of Signal Transduction, NIEHS, NIH, DHHS, Research Triangle Park
  • , Angelika ZarembaAffiliated withInositol Signaling Section, Laboratory of Signal Transduction, NIEHS, NIH, DHHS, Research Triangle Park
  • , Yixing ZhouAffiliated withInositol Signaling Section, Laboratory of Signal Transduction, NIEHS, NIH, DHHS, Research Triangle Park

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Abstract

Ins(1,4,5)P3 is a classical intracellular messenger: stimulus-dependent changes in its levels elicits biological effects through its release of intracellular Ca2+ stores. The Ins(1,4,5)P3 response is “switched off” by its metabolism to a range of additional inositol phosphates. These metabolites have themselves come to be collectively described as a signaling “family”. The validity of that latter definition is critically examined in this review. That is, we assess the strength of the hypothesis that Ins(1,4,5)P3 metabolites are themselves “classical” signals. Put another way, what is the evidence that the biological function of a particular inositol phosphate depends upon stimulus dependent changes in its levels? In this assessment, examples of an inositol phosphate acting as a cofactor (i.e. its function is not stimulus-dependent) do not satisfy our signaling criteria. We conclude that Ins(3,4,5,6)P4 is, to date, the only Ins(1,4,5)P3 metabolite that has been validated to act as a second messenger.

Keywords

Adenosine deaminase AKT b-cells Calcium cAMP CaMKII Chloride channel ClC3 Compartmentalization DNA repair Endosomes ERK Frizzled receptor GAP1IP4BP mRNA export Ins(1,4,5)P3 Ins(1,4,5)P3 receptor Ins(1,3,4)P3 Ins(1,3,4,5)P4 Ins(1,3,4,5)P4 receptor Ins(1,4,5,6)P4 Ins(3,4,5,6)P4 Ins(1,3,4,5,6)P5 InsP6 Insulin IPMK IPK2 IP5K ITP ITPK1 ITPKB Lymphocytes Ku Neutrophils Protein phosphatase PtdIns(4,5)P2 PtdIns(3,4,5)P3 PH domain PTEN RASA3 Transcription Wnt ligand