Wnt regulation of beta-catenin degradation is essential for development and carcinogenesis. beta-catenin degradation is initiated upon amino-terminal serine/threonine phosphorylation, which is believed to be performed by glycogen synthase kinase-3 (GSK-3) in complex with tumor suppressor proteins Axin and adnomatous polyposis coli (APC). Here we describe another Axin-associated kinase, whose phosphorylation of beta-catenin precedes and is required for subsequent GSK-3 phosphorylation of beta-catenin. This "priming" kinase is casein kinase Ialpha (CKIalpha). Depletion of CKIalpha inhibits beta-catenin phosphorylation and degradation and causes abnormal embryogenesis associated with excessive Wnt/beta-catenin signaling. Our study uncovers distinct roles and steps of beta-catenin phosphorylation, identifies CKIalpha as a component in Wnt/beta-catenin signaling, and has implications to pathogenesis/therapeutics of human cancers and diabetes.

Novel nanomaterials for bioassay applications represent a rapidly progressing field of nanotechnology and nanobiotechnology. Here, we present an exploration of single-walled carbon nanotubes as a platform for investigating surface-protein and proteinprotein binding and developing highly specific electronic biomolecule detectors. Nonspecific binding on nanotubes, a phenomenon found with a wide range of proteins, is overcome by immobilization of polyethylene oxide chains. A general approach is then advanced to enable the selective recognition and binding of target proteins by conjugation of their specific receptors to polyethylene oxide-functionalized nanotubes. This scheme, combined with the sensitivity of nanotube electronic devices, enables highly specific electronic sensors for detecting clinically important biomolecules such as antibodies associated with human autoimmune diseases. R ecent years have witnessed significant interest in biological applications of novel inorganic nanomaterials such as nanocrystals (1, 2), nanowires (3), and nanotubes (4, 5) with the motivation to create new types of analytical tools for life science and biotechnology. Single-walled carbon nanotubes (SWNTs) are interesting molecular wires (diameter Ϸ1-2 nm) with unique electronic properties that have been spotlighted for future solid-state nanoelectronics (6, 7). Bridging nanotubes with biological systems, however, is a relatively unexplored area, with the exception of a few reports on nanotube probe tips for biological imaging (4), nonspecific binding (NSB) of proteins (8-10), functionalization chemistry for bioimmobilization on nanotube sidewalls (5), and one study on biocompatibility (11).Previously, we and others have shown that the electrical conductance of a nanotube is highly sensitive to its environment and varies significantly with changes in electrostatic charges and surface adsorption of various molecules (12)(13)(14). This research has hinted at possible SWNT-based miniature sensors for detecting biological molecules in fluids. Here, we systematically explore how nanotubes interact with and respond to various proteins in solution, how chemical functionalization can be used to tailor these interactions, and how the resulting understanding enables highly selective nanotube sensors for the electronic detection of proteins. Using atomic force microscopy (AFM) and quartz crystal microbalance (QCM) and electronic transport measurements, we first reveal that proteins in general exhibit a high degree of NSB on nanotubes, a phenomenon undesirable for potential biosensors. We then demonstrate a functionalization scheme involving irreversible adsorption of Tween 20 or triblock copolymer chains on nanotubes to prevent this general NSB, while at the same time enabling the binding of specific proteins of interest that can be detected electronically without the need for labeling. Further, we demonstrate specific detection of mAbs to the human autoantigen U1A, a prototype target of the autoimmune response in patients with systemic lupu...

Carbon nanotube field-effect transistors commonly comprise nanotubes lying on SiO 2 surfaces exposed to the ambient environment. It is shown here that the transistors exhibit hysteresis in their electrical characteristics because of charge trapping by water molecules around the nanotubes, including SiO 2 surface-bound water proximal to the nanotubes. Hysteresis persists for the transistors in vacuum since the SiO 2bound water does not completely desorb in vacuum at room temperature, a known phenomenon in SiO 2 surface chemistry. Heating under dry conditions significantly removes water and reduces hysteresis in the transistors. Nearly hysteresis-free transistors are obtainable by passivating the devices with polymers that hydrogen bond with silanol groups on SiO 2 (e.g., with poly(methyl methacrylate) (PMMA)). However, nanotube humidity sensors could be explored with suitable water-sensitive coatings. The results may have implications to field-effect transistors made from other chemically derived materials.

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