Independent effects of colour on object identification and memory

We examined the effects of colour on object identification and memory using a study–test priming procedure with a coloured-object decision task at test (i.e., deciding whether an object is correctly coloured). Objects were selected to have a single associated colour and were either correctly or incorrectly coloured. In addition, object shape and colour were either spatially integrated (i.e., colour fell onthe object surface) or spatially separated (i.e., colour formed the background to the object). Transforming the colour of an object from study to test (e.g., from a yellow banana to a purple banana) reduced priming of response times, as compared to when the object was untransformed. This utilization of colour information in object memory was not contingent upon colour falling on the object surface or whether the resulting configuration was of a correctly or incorrectly coloured object. In addition, we observed independent effects of colour on response times, whereby coloured-object decisions were more efficient for correctly than for incorrectly coloured objects but only when colour fell on the object surface. These findings provide evidence for two distinct mechanisms of shape–colour binding in object processing

Inhibition of IFN-α signaling by a PKC- and protein tyrosine phosphatase SHP-2-dependent pathway

Cytokine signaling by the Jak–STAT pathway is subject to complex negative regulation that limits the amplitude and duration of signal transduction. Inhibition of signaling also mediates negative crosstalk, whereby factors with opposing biological activities crossinhibit each other's function. Here, we investigated a rapidly inducible mechanism that inhibited Jak–STAT activation by IFN-α, a cytokine that is important for antiviral responses, growth control, and modulation of immune responses. IFN-α-induced signaling and gene activation were inhibited by ligation of Fc receptors and Toll-like receptors 7 and 8 in a PKCβ-dependent manner. Neither PKCβ nor PKCδ influenced responses of cells treated with IFN-α alone. Inhibition of IFN-α signaling correlated with suppression of IFN-α-dependent antiviral responses. PKC-mediated inhibition did not require de novo gene expression but involved the recruitment of PKCβ to the IFN-α receptor and interaction with protein tyrosine phosphatase SHP-2, resulting in augmented phosphatase activity. PKC-mediated inhibition of IFN-α signaling was abolished in SHP-2-deficient cells, demonstrating a pivotal role for SHP-2 in this inhibitory pathway. Together, our data describe a rapidly inducible, direct mechanism of inhibition of Jak–STAT signaling mediated by a PKCβ–SHP-2 signaling pathway

STIM1, PKC-δ and RasGRP set a threshold for proapoptotic Erk signaling during B cell development

Clonal deletion of autoreactive B cells is crucial for the prevention of autoimmunity, but the signaling mechanisms that regulate this checkpoint remain undefined. Here we characterize a previously unrecognized Ca(2+)-driven pathway for activation of the kinase Erk, which was proapoptotic and biochemically distinct from Erk activation induced by diacylglycerol (DAG). This pathway required protein kinase C-δ (PKC-δ) and the guanine nucleotide-exchange factor RasGRP and depended on the concentration of the Ca(2+) sensor STIM1, which controls the magnitude of Ca(2+) entry. Developmental regulation of these proteins was associated with selective activation of the pathway in B cells prone to negative selection. This checkpoint was impaired in PKC-δ-deficient mice, which developed B cell autoimmunity. Conversely, overexpression of STIM1 conferred a competitive disadvantage to developing B cells. Our findings establish Ca(2+)-dependent Erk signaling as a critical proapoptotic pathway that mediates the negative selection of B cells