title: Defining signal transduction by inositol phosphates.
abstract: Ins(1,4,5)P(3) is a classical intracellular messenger: stimulus-dependent changes in its levels elicits biological effects through its release of intracellular Ca(2+) stores. The Ins(1,4,5)P(3) 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)P(3) 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)P(4) is, to date, the only Ins(1,4,5)P(3) metabolite that has been validated to act as a second messenger.
authors.affiliation: Inositol Signaling Section, Laboratory of Signal Transduction, NIEHS, NIH, DHHS, Research Triangle Park, 27709, NC, USA, USA, shears@niehs.nih.gov.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Shears
authors.forename: Sindura B
authors.initials: SB
authors.lastname: Ganapathi
authors.forename: Nikhil A
authors.initials: NA
authors.lastname: Gokhale
authors.forename: Tobias M H
authors.initials: TM
authors.lastname: Schenk
authors.forename: Huanchen
authors.initials: H
authors.lastname: Wang
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Weaver
authors.forename: Angelika
authors.initials: A
authors.lastname: Zaremba
authors.forename: Yixing
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D005057:Eukaryotic Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D015290:Second Messenger Systems
chemical_list: D007295:Inositol Phosphates; C081652:inositol-3,4,5,6-tetrakisphosphate; D015544:Inositol 1,4,5-Trisphosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); C051038:Inositol 1,4,5-trisphosphate 3-kinase; D002118:Calcium