Cyclin‐dependent kinases (cdk) play an essential role in the intracellular control of cell division cycle (cdc). These and their regulators are frequently deregulated human tumours. Enzymatic screening has recently led to discovery specific inhibitors cyclin‐dependent kinases, such as butyrolactone I, flavopiridol purine olomoucine. Among a series C2, N 6 , N9‐substituted ade‐nines tested on purified cdc2/cylin B, 2‐(1‐ethyl‐2‐hydroxyethylamino)‐6‐benzylamino‐9‐isopropylpu‐rine (roscovitine)...

Abstract Detailed information on innervation of the histaminergic system in brain is essential to an understanding physiological roles this system. In a previous immunocytochemical study with antihistidine decarboxylase (HDC) antibody, we detected extensive networks fibers many areas rat (Watanabe et al., ′84). present study, improved procedure and examined detailed distribution anti‐HDC antibody. As reported previously, highest concentrations were found hypothalamic nuclei medial forebrain...

We previously identified Rho-associated protein kinase (Rho-kinase) as a specific effector of Rho. In this study, we collapsin response mediator protein-2 (CRMP-2), novel Rho-kinase substrate in the brain. CRMP-2 is neuronal whose expression up-regulated during development. phosphorylated at Thr-555 <i>in vitro.</i> produced an antibody that specifically recognizes Thr-555. Using antibody, found downstream Rho COS7 cells. Phosphorylation was observed chick dorsal root ganglion neurons...

THE effects of neurotrophins on intracellular Ca2+ levels in rat hippocampal neurones were studied vitro using fura-2 fluorescence microscopy. BDNF and NT-3, but not NGF, rapidly increased cytoplasmic concentrations these ten-fold to reach 1 μM. Moreover some the both NT-3 elicited responses, indicative presence functional receptors for same cell. In cultures approximately 80% stained with antibodies against full-length Trk B. The expression B was also confirmed by RNA analysis. These...

Abstract Site‐specific phosphorylation of intermediate filament (IF) proteins on serine and threonine residues leads to alteration the structure, in vitro vivo . Protein kinases involved cell signaling those activated mitosis dynamically control spatial temporal organization intracellular IF phosphorylation. Thus, appears be one most predominant strategies coordinating network.

The growth cone, a motile structure located at the tip of growing axons, senses extracellular guidance cues and translates them into directional forces that drive axon outgrowth guidance. Axon directed by chemical on adhesive substrate is termed haptotaxis. Recent studies reported netrin-1 functions as haptotactic cue. However, mechanism mediating netrin-1–induced axonal haptotaxis remains unclear. Here, we demonstrate substrate-bound induces facilitating physical interactions between...

Rho-associated kinase (Rho-kinase), which is activated by the small GTPase Rho, regulates formation of stress fibers and focal adhesions, myosin fiber organization, neurite retraction through phosphorylation cytoskeletal proteins, including light chain, ERM family proteins (ezrin, radixin, moesin) adducin. Rho-kinase was found to phosphorylate a type III intermediate filament (IF) protein, glial fibrillary acidic protein (GFAP), exclusively at cleavage furrow during cytokinesis. In present...

TrkB belongs to the Trk family of tyrosine kinase receptors and mediates response brain-derived neurotrophic factor (BDNF) neurotrophin-4/5 (NT-4/5). Here, we report that both truncated full-length forms are expressed in developing cerebellar granule neurons. BDNF NT-4/5 increased survival cultured also induced an autophosphorylation subsequently resulted a phosphorylation binding phospholipase C-gamma (PLC-gamma) SH2-containing sequence autophosphorylated receptors. Both contain src...

Neurons have the remarkable ability to polarize even in symmetrical vitro environments. Although recent studies shown that asymmetric intracellular signals can induce neuronal polarization, it remains unclear how these polarized are organized without cues. We describe a novel protein, named shootin1, became up-regulated during polarization of hippocampal neurons and began fluctuating accumulation among multiple neurites. Eventually, shootin1 accumulated asymmetrically single neurite, which...

Actin polymerizes near the leading edge of nerve growth cones, and actin filaments show retrograde movement in filopodia lamellipodia. Linkage between filament flow cell adhesion molecules (CAMs) cones is thought to be one mechanisms for axon outgrowth guidance. However, molecular basis this linkage remains elusive. Here, we that shootin1 interacts with both L1-CAM axonal cultured rat hippocampal neurons, thereby mediating them. Impairing linkage, either by RNA interference or disturbing...

Actin and actin-associated proteins migrate within various cell types. To uncover the mechanism of their migration, we analyzed actin waves, which translocate along neuronal axons toward growth cones. We found that arrays filaments constituting waves undergo directional assembly disassembly, with polymerizing ends oriented axonal tip, lateral side is mechanically anchored to adhesive substrate. A combination live-cell imaging, molecular manipulation, force measurement, mathematical modeling...

Motile cells transduce environmental chemical signals into mechanical forces to achieve properly controlled migration. This signal–force transduction is thought require regulated coupling between actin filaments (F-actins), which undergo retrograde flow at the cellular leading edge, and cell adhesions via linker “clutch” molecules. However, molecular machinery mediating this regulatory remains unclear. Here we show that F-actin binding molecule cortactin directly interacts with a clutch...

Although accumulating data reveal patterns of proliferation, migration, and differentiation neuronal lineage cells in the developing brain, gliogenesis brain has not been well elucidated. In rat vimentin is selectively expressed radial glia their progeny, oligodendrocytes or neurons from embryonic day 15 (E15) until postnatal (P15). Here we examined mitotic glial E17–P7, using monoclonal antibody 4A4, which recognizes phosphorylated by a mitosis-specific kinase, cdc2 kinase. neocortex,...

Insulin-like growth factor (IGF)-1 plays crucial roles in control and rearrangements of the cytoskeleton. IGF-1 binds to receptor thereby induces autophosphorylation this at its tyrosine residues. The phosphorylation is thought initiate a cascade events. Although various signaling molecules have been identified, they appear interact with tyrosine-phosphorylated receptor. Here, we identified leukemia-associated Rho guanine nucleotide exchange (GEF) (LARG), which contains PSD-95/Dlg/ZO-1...