Defining signal transduction by inositol phosphates.
Stephen B Shears1, Sindura B Ganapathi, Nikhil A Gokhale
1Inositol Signaling Section, Laboratory of Signal Transduction, NIEHS, NIH, DHHS, Research Triangle Park, 27709, NC, USA, USA, shears@niehs.nih.gov.
Sub-Cellular Biochemistry
|March 1, 2012
Summary
Inositol trisphosphate (Ins(1,4,5)P(3)) metabolites are not classical signals, except for Ins(3,4,5,6)P(4). This review assesses if Ins(1,4,5)P(3) metabolites function as second messengers.
Area of Science:
- Cellular signaling
- Biochemistry
- Molecular biology
Background:
- Inositol trisphosphate (Ins(1,4,5)P(3)) is a key intracellular messenger regulating calcium (Ca2+) release.
- Ins(1,4,5)P(3) is metabolized into various inositol phosphates, forming a signaling "family".
Purpose of the Study:
- To critically evaluate the hypothesis that Ins(1,4,5)P(3) metabolites function as classical signaling molecules.
- To determine if the biological roles of these metabolites are dependent on stimulus-induced changes in their levels.
Main Methods:
- Review of existing literature on inositol phosphate metabolism and function.
- Assessment of evidence for stimulus-dependent changes in metabolite levels and their biological effects.
- Distinguishing between second messenger roles and cofactor functions.
Main Results:
- Most Ins(1,4,5)P(3) metabolites do not meet the criteria for classical second messengers.
- Examples of metabolites acting solely as cofactors were excluded from signaling criteria.
- Ins(3,4,5,6)P(4) is the only metabolite validated as a second messenger to date.
Conclusions:
- The definition of the Ins(1,4,5)P(3) metabolite "family" as classical signals requires stringent validation.
- Only Ins(3,4,5,6)P(4) has demonstrated classical second messenger activity.
- Further research is needed to fully elucidate the signaling roles of other inositol phosphates.
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