Abstract
In the not too distant past, the very large and still growing family of signaling kinases could be neatly subdivided into two broad classes, those that phosphorylated lipids and those that used proteins as substrates. Investigators who focused on protein kinases rarely crossed ideological paths with researchers involved in lipid kinase research. However, as is often the case in modern-day cell biology, the conceptual division of ATP-binding phosphotransferases into lipid kinases and protein kinases has proved an oversimplification of the chaotic reality that typifies the process of intracellular signaling. First, we were surprised to learn that certain bona fide lipid kinases, specifically the phosphoinositide 3-kinases (PI3Ks), were quite capable of phosphorylating a limited spectrum of protein substrates, at least when pressed to do so under in vitro conditions. Then, during the mid-1990s, the molecular cloning efforts of several laboratories further confused the picture with the identification of a novel family of high molecular mass kinases whose catalytic domains bore a clear resemblance to those of PI3Ks. Based on this primary sequence homology, the newly identified kinases were named PI3Krelated kinases (PIKKs). The expectation at the time was that the PIKK family members would relay signals, at least in part, through the phosphorylation of inositol phospholipids. Instead, it now appears that evolution has brought us full circle—in spite of the lipid kinase-like catalytic domain, the PIKKs apparently have dedicated themselves fully to the phosphorylation of protein substrates.
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Tibbetts, R.S., Abraham, R.T. (2000). PI3K-Related Kinases. In: Gutkind, J.S. (eds) Signaling Networks and Cell Cycle Control. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-218-0_15
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