Dear Colleagues,

Enzymes catalyzing the generation of 3-phosphorylated phosphoinositides were discovered in 1989 [1]. Ten years later, this special enzymatic activity could be assigned to PI3K, a family of structurally-defined signaling proteins [2]. Based on shared enzymatic products and structural similarities of PI3K, similar biological functions of these proteins have been expected. Current insights challenge this simplified belief. Apparently, PI3K are able to impact basically all biological processes.

A striking example of the functional promiscuity of PI3K is the ongoing discussion about regulatory functions of the PI3K species PI3Kγ. PI3Kγ is strongly expressed in leukocytes and has been described as a key mediator of both pro-inflammatory [3,4] and anti-inflammatory processes [5]. These contradictory findings provoke questions of the validity of current heuristic approaches in signaling research.

In the planed anthology, we aim to examine puzzling experimental results on PI3K signaling in cells and organisms. Specifically, we propose to explore and to discuss the following topics:

- Complex functional patterns mediated by enzymatic and non-enzymatic activities of PI3K.
- Contradictory data sets about the functioning of PI3K species.
- Adaptive, possibly “hormetic” responses of PI3K signaling to different environmental conditions.

We especially suggest highlighting teleological approaches for the discussion of recent PI3K signaling data. The selection advantage of specific PI3K functions could be questioned. The idea of a “Signaling Darwinism” might be useful for the design of future signaling research after all.

Prof. Dr. Reinhard Wetzker
Guest Editor

References

1. Whitman, M.; Downes, C.P.; Keeler, M.; Keller, T.; Cantley, L. Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate. Nature 1988, 332, 644–646.
2. Vanhaesebroeck, B.; Leevers, S.J.; Panayotou, G.; Waterfield, M.D. Phosphoinositide 3-kinases: A conserved family of signal transducers. Trends Biochem. Sci. 1997, 22, 267–272.
3. Hirsch, E.; Katanaev, V,L.; Garlanda, C.; Azzolino, O.; Pirola, L.; Silengo, L.; Sozzani, S.; Mantovani, A.; Altruda, F.; Wymann, M.P. Central role for G protein-coupled phosphoinositide 3-kinase gamma in inflammation. Science 2000, 287, 1049–1053.
4. Rückle, T.; Schwarz, M.K.; Rommel, C. PI3Kgamma inhibition: Towards an 'aspirin of the 21st century'? Nat. Rev. Drug Discov. 2006, 5, 903–918.
5. Kaneda, M.M.; Messer, K.S.; Ralainirina, N.; Li, H.; Leem, C.J.; Gorjestani, S.; Woo, G.; Nguyen, A.V.; Figueiredo, C.C.; Foubert, P.; et al. PI3Kγ is a molecular switch that controls immune suppression. Nature 2016, 539, 437–442.

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• PI3K
• signaling
• complex functional patterns
• contradictory results
• adaptive responses