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The p66shc protein governs oxidant stress and mammalian lifespan. Here, we identify melanoma inhibitory activity (MIA), a protein secreted by melanoma cells, as a novel binding partner and antagonist of p66shc. The N-terminal collagen homology-2 (CH2) domain of p66shc binds to the Src Homology-3 (SH3)-like domain of MIA in vitro. In cells, ectopically expressed MIA and p66shc colocalize and co-precipitate. MIA also co-precipitates with the CH2 domain of p66shc in vivo. MIA expression in vivo suppresses p66shc-stimulated increase in endogenous hydrogen peroxide (H(2)O(2)), and inhibits basal and H(2)O(2)-induced phosphorylation of p66shc on serine 36 and H(2)O(2)-induced death. In human melanoma cells expressing MIA, endogenous MIA and p66shc co-precipitate. Downregulation of MIA in melanoma cells increases basal and ultraviolet radiation (UVR)-induced phosphorylation of p66shc on serine 36, augments endogenous H(2)O(2) levels, and increases their susceptibility to UVR-induced death. These findings show that MIA binds to p66shc, and suggest that this interaction antagonizes phosphorylation and function of p66shc.

Abstract: 7–12Hz Oscillations, characterized by spindle-like high-voltage rhythmic spike components, appear in quiet immobile states of rats. However, it remains unclear what their relationships with preceding behavioral activities are and how prefrontal neuronal dynamics during these oscillations is. In the present study, we first determined the relationship of 7–12Hz oscillations with the wake–sleep cycle and preceding behavioral activities in several normal rat strains by recording electroencephalograms from the multiple cortical regions. Prolonged awake period transiently enhanced the following appearance of 7–12Hz oscillations, which were frequently followed by slow-wave sleep. The degree of transient enhancement under the task condition was similar to that by prolonged wakefulness under the no-task condition. In addition, by recording local-field potential and multi-unit activities in the medial prefrontal cortex, we determined the temporal dynamics of prefrontal neuronal activities in relation to 7–12Hz oscillations. Collective neuronal activities in medial prefrontal cortex were gradually organized into phase-locked patterns and showed highly synchronization during these oscillations. These dynamics were in temporal proximity to those of slow-wave activities (<4Hz). Since slow-wave activities are thought to synchronize large spatial domains, these results suggest that 7–12Hz oscillations are involved in the transition from the awake to sleep states by oscillatory entrainment of global cortical networks including the prefrontal neurons. [Copyright &y& Elsevier]

We applied a differential display PCR technique to isolate molecules that are area-specific in expression in the primate neocortex, and found that growth/differentiation factor 7 (GDF7), a member of the bone morphogenetic protein (BMP)/transforming growth factor (TGF) beta super-family, is preferentially expressed in the primary motor area of African green monkeys (Cercopithecus aethiops). We proved that GDF7 is 10 times more abundant in the motor cortex than in the visual cortex by northern blotting and quantitative RT-PCR. When we examined the neocortex of closely related rhesus monkeys (Macaca mulatta), GDF7 was also most abundant in the motor cortex, although the regional difference was reduced to 3-fold. This differential expression pattern was observed in both newborn and infant rhesus monkeys. We found that several type I/II receptors of BMP, candidates of the receptors for GDF7, are uniformly expressed in the mature neocortex. The unique expression pattern of GDF7 suggests that it may play an active role in the motor area of the primate neocortex. [ABSTRACT FROM AUTHOR]

Objective and Design: To further understand the mechanisms of signal transduction pathways for the formation of F-actin (polymerization of actin) and the activation of NADPH oxidase in phagocytic cells, the effects of various inhibitors on them were studied.¶ Materials and Methods: Differentiated HL60 cells were studied to examine their N-formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated formation of F-actin and activation of NADPH oxidase following treatment with various inhibitors. These included a protein kinase C (PKC) inhibitor (GF 109203X), a phosphatidylinositide 3 kinase (PI3-K) inhibitor (wortmannin), an extracellular response kinase (ERK) inhibitor (PD 98059), a p38 mitogen-activated protein kinase (MAPK) inhibitor (SB 203580) and an intracellular Ca2+-chelator (BAPTA-AM).¶ Results: The treatment with wortmannin suppressed the formation of F-actin, with less suppression of the activation of NADPH oxidase. BAPTA-AM and GF 109203X did not attenuate the formation of F-actin but completely inhibited the activation of NADPH oxidase. PD 98059 and SB 203580 partially inhibited the activation of NADPH oxidase without influence on the formation of F-actin. Furthermore, wortmannin but not BAPTA-AM and GF 109203X inhibited the fMLP-induced activation of Akt, which is known to regulate NADPH oxidase.¶ Conclusions: These results suggest that the formation of F-actin is dependent on PI3-K and independent of PKC, ERK and p38 MAPK as well as the increase in intracellular Ca2+, whereas the activation of NADPH oxidase is partly dependent on ERK, p38 MAPK, Akt regulated by PI3-K, and strongly dependent on the activation of PKC and the increase in intracellular Ca2+.¶ [ABSTRACT FROM AUTHOR]

Describes the characteristics of a protein secreted by cultured rat heart cells that can direct the choice of neurotransmitter phenotype made by cultured rat sympathetic neurons. This protein is identical to a protein that can inhibit the proliferation and induce macrophage differentiation of the leukemia inhibitory factor, also known as D factor. Protein sequencing method; Cloning method.