Protein kinases signal transduction pathways, study

Protein kinase signal transduction pathways have been extensively studied and characterized in the myocardium. Ischemic preconditioning (IP) and the role of individual kinases involved is where much of the research efforts have been focused. IP is the reduction in susceptibility to myocardial infarction that follows brief periods of sublefhal ischemia (Murry et al, 1986). This reduction can manifest itself as a 4-fold reduction in infarct size, this being secondary to a delay in the onset and rate of cell necrosis during the subsequent lethal ischemia (Marber et al., 1994). 

Src is the prototype of the superfamily of protein tyrosine kinases and was one of the first protein kinases to be characterized by various genetic, cellular, and structure-function studies to help imderstand its role in signal transduction pathways as well as in disease processes, including cancer, osteoporosis, and both tumor- and inflammation-mediated bone loss [28-38]. In fact, studies on Src provided some of the first evidence correlating protein kinase activity and substrate protein phosphorylation in the regulation of signal transduction pathways relative to normal cellular activity as well as mahgnant transformations. Src family kinases include Fyn, Yes, Yrk, Blk, Fgr, Hck, Lyn,... 

Role of endogenously activated type 1, protein phosphatese 1 (PPl) and type 2A (PP2A) in the signal transduction pathway of PAF stimulated rabbit platelets has been studied. Calyculin A, an inhibitor of PPl and PP2A, caused inhibition of Ca influx by PAF and correlated with inhibition of Ins (1,4,5) P, formation (Muiphy and Westwick, 1994). It is therefore abundantly clear that both PKC and tyrosine kina% are integral components of PAF receptor signaling pathways. PAF is one of the first G-protein coupled receptors reported to be coupled to tyrosine kinase (Dhar et.al. 1990). 

More recent research has focused on examining underlying commonalities in the biochemical actions of the mood stabilizers used to treat bipolar disorder (Zhou et al., 2005), in studies of postmortem brain tissue (Post et al., 2003), and in signal transduction pathways and regulation of gene expression (Bezchlibnyk and Young, 2002). For example, altered levels or function of G-protein alpha subunits and protein kinase A and C have been found in bipolar patients, as well as disruption in second messenger cascades such as the ERK/MAPK pathways. 

The studies of mast cell cytokine production described above have shown that maximal induction of cytokine synthesis and release usually occurs in response to IgE-dependent activation. In common with many cell types, there is evidence that FccRI on mast cells is coupled to the phospholipase C effector system that controls two distinct signal transduction pathways, one regulated by Ca " ions and the other by protein kinase C (PKC). Exocytotic degranulation is associated with an increased cytoplasmic level of Ca ions, and activation of mast cells can be therefore achieved by the use of calcium iono-phores which raise intracellular calcium concentrations through a receptor-independent mechanism. Alternative mast cell stimuli include phorbol-12-myristate-13-acetate (PMA) which activates PKC and induces mediator secretion from basophils and rodent mast cells but not from human mast cells, and concanavalin A (Con A), a lectin which can stimulate mast cells by cross-linking of cell-bound IgE and/or cell surface glycoproteins. 

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