Tolerance induction by allogeneic hematopoietic stem cells

In this issue of Cell Stem Cell, Zheng et?al. (2011) report that HSCs expressing PD-L1 display enhanced engraftment in irradiated allogeneic recipients. Independently in Nature, Fujisaki et?al. (2011) observe allogeneic HSCs persisting in proximity to regulatory T?cells in nonirradiated recipients, further connecting HSCs and immune tolerance.     

G-proteins and second messengers in mitogenesis

Growth factors stimulate mitogenesis via the generation of signal molecules or events. Transduction of these messages into the cell proceeds by the binding of the mitogen to a specific cell surface receptor which then stimulates the effector system (enzyme, ion channel, etc.) via a guanine nucleotide binding regulatory protein (G-protein). The specificity of a particular G-protein is a function of its unique α-subunit. This article reviews the effects of different growth factors upon second mesenger generation and discusses the involvement of the different G-proteins in these signal transduction pathways.     

Stimulation of mechano-growth factor expression by second messengers

The effect of second messengers on the expression of mechano-growth factor (MGF) synthesis by myoblasts and differentiated myotubes in culture was investigated. cAMP stimulates MGF expression both in murine and human cells. CNG- and HCN-channel blockers slightly activated MGF synthesis, while an activator of Epac protein had no effect. It is assumed that cAMP activates MGF synthesis via protein kinase A. Phorbol ester (PMA) activates MGF synthesis in human myoblasts and myotubes only. The expression of another splice form of IGF-1 gene, IGF-1Ea, was also stimulated in human cells by db-cAMP and PMA and in murine cells by db-cAMP only. Stimulation of MGF expression in human cells by db-cAMP and PMA demonstrated different time dependences but showed additivity when the compounds were applied in a combination. Inhibitors specific to protein kinase A did not affect PMA-mediated activation, while inhibitors specific to protein kinase C did not affect db-cAMP-mediated process. Ca²⁺ ionophore and ROS inductor strongly inhibited synthesis of the growth factor. PGE2 known as physiological stimulator of cAMP synthesis was shown to stimulate MGF expression both in murine and human cells. Implication of protein kinase A and protein kinase C in MGF synthesis stimulation and a cross-talk between two signaling systems is discussed.     

Generation of second messengers in Plasmodium

Signalling in malaria parasites is a field of growing interest as its components may prove to be valuable drug targets, especially when one considers the burden of a disease that is responsible for up to 500 million infections annually. The scope of this review is to discuss external stimuli in the parasite life cycle and the upstream machinery responsible for translating them into intracellular responses, focussing particularly on the calcium signalling pathway.