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Updated: Aug 30, 2026

Single-molecule Super-resolution Imaging of Phosphatidylinositol 4,5-bisphosphate in the Plasma Membrane with Novel Fluorescent Probes
Published on: October 15, 2016
BTK regulates PtdIns-4,5-P2 synthesis: importance for calcium signaling and PI3K activity
Kan Saito1, Kimberley F Tolias, Abdelhafid Saci
1Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
Abstract:
Intracellular signaling by most cell surface receptors requires the generation of two major second messengers, phosphatidylinositol-3,4,5-trisphosphate (PtdIns-3,4,5-P3) and inositol-1,4,5-trisphosphate (IP3). The enzymes that produce these second messengers, phosphoinositide 3-kinase (PI3K) and phospholipase C (PLC), utilize a common substrate, phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P2). Until now, it has not been clear whether de novo PtdIns-4,5-P2 synthesis is necessary for PtdIns-3,4,5-P3 and IP3 production. Here we show that BTK, a member of the Tec family of cytoplasmic protein tyrosine kinases, associates with phosphatidylinositol-4-phosphate 5-kinases (PIP5Ks), the enzymes that synthesize PtdIns-4,5-P2. Upon B cell receptor activation, BTK brings PIP5K to the plasma membrane as a means of generating local PtdIns-4,5-P2 synthesis. This enzyme-enzyme interaction provides a shuttling mechanism that allows BTK to stimulate the production of the substrate required by both its upstream activator, PI3K, and its downstream target, PLC-gamma2.
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