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The effects of protein phosphatases on single cystic fibrosis transmembrane conductance regulator (CFTR) channels exposed to comparable levels of phosphatase activity were characterized. The objective of the research was to evaluate the ability of PP2C and other protein phosphatases to downregulate the CFTR and deactivate CFTR channels in the epithelial cell line. Results indicate that PP2C is a potent regulator of CFTR activity. Its effects are comparable to those of endogenous phosphatases in CHO, BHK and T84 epithelial cells but different from those of PP2A.

Role of protein phosphatases in the activation of CFTR (ABCC7) by genistein and bromotetramisole. Am J Physiol Cell Physiol 279: C108-C119, 2000.--Genistein and bromotetramisole (Br-t) strongly activate cystic fibrosis transmembrane conductance regulator (CFTR; ABCC7) chloride channels on Chinese hamster ovary cells and human airway epithelial cells. We have examined the possible role of phosphatases in stimulation by these drugs using patch-clamp and biochemical methods. Genistein inhibited the spontaneous rundown of channel activity that occurs after membrane patches are excised from cAMP-stimulated cells but had no effect on purified protein phosphatase type 1 (PP1), PP2A, PP2B, PP2C, or endogenous phosphatases when assayed as [[sup.32]P][PO.sub.4] release from prelabeled casein, recombinant GST-R domain fusion protein, or immunoprecipitated full-length CFTR. Br-t also slowed rundown of CFTR channels, but, in marked contrast to genistein, it did inhibit all four protein phosphatases tested. Half-maximal inhibition of PP2A and PP2C was observed with 0.5 and 1.5 mM Br-t, respectively. Protein phosphatases were also sensitive to (+)-p-Br-t, a stereoisomer of Br-t that does not inhibit alkaline phosphatases. Br-t appeared to act exclusively through phosphatases since it did not affect CFTR channels in patches that had low apparent endogenous phosphatase activity (i.e., those lacking spontaneous rundown). We conclude that genistein and Br-t act through different mechanisms. Genistein stimulates CFTR without inhibiting phosphatases, whereas Br-t acts by inhibiting a membrane-associated protein phosphatase (probably PP2C) that presumably allows basal phosphorylation to accumulate. cystic fibrosis; phosphorylation; PP2C; (iso)flavonoids; phenylimidazothiazoles; cystic fibrosis transmembrane conductance regulator

Tunnel-Diode Body-Contact (TDBC) SOI MOSFETs utilize a shallow source and a deep drain to eliminate total-ionizing-dose induced back-channel leakage and to suppress floating body effects. In contrast, significant leakage current is observed in T-gate Body-Contact (TB) SOI nMOSFETs, as a result of trapped charge in the buried oxide. A subthreshold hump is observed in TDBC SOI nMOSFETs after irradiation. The charge trapped at the shallow trench isolation (STI) corner is the major reason for the post-irradiation hump in the current-voltage characteristics. Pocket p^ + implantation reduces the size of the subthreshold hump in short-channel TDBC devices. [ABSTRACT FROM PUBLISHER]

A tunnel diode body contact (TDBC) silicon-oninsulator (SOI) MOSFET structure without floating-body effects (FBEs) is proposed and successfully demonstrated. The key idea of the proposed structure is that a tunnel diode is embedded in the source region, so that the accumulated carriers can be released through tunneling. In an n-MOSFET, a heavily doped \p^+ layer is introduced beneath the \n^+ source region. The simulated and measured results show the suppressed FBE, as expected. Other phenomena that originate from the FBEs, such as the kink, linear kink effect, abnormal subthreshold swing, and small drain-tosource breakdown voltage in the properties, were also sufficiently suppressed. In addition, it should be noted that the proposed SOI MOSFETs are fully laid out and process compatible with SOI CMOS. Hysteresis effects disappear in TDBC SOI MOSFETs, which makes them attractive for digital applications. On the other hand, in analog applications, TDBC SOI MOSFETs are shown to hold the advantage over floating-body SOI MOSFETs due to their higher Gm/ID ratio. TDBC SOI MOSFETs can be considered as one of the promising candidates for digital and analog devices. [ABSTRACT FROM PUBLISHER]