Cell membrane, protein kinase

From the structural and in vitro biological data summarized in this review, we can conclude that MSP is a growth and motility factor that activates a typical cell membrane protein tyrosine kinase receptor. However, despite an... 

MAPK translocates to the surface membrane before contraction and then redistributes to the cytoplasm coincident with muscle cell shortening. Protein kinase C inhibitors block these translocations, suggesting a role for PKC in the activation of MAPK. In further support of a role for PKC in this process, PKC translocates to the surface membrane at the same time as MAPK. 

Every cell contains protein kinases. Sometimes several different protein kinases are found in the same cells. Although it has not been established that all protein kinases are activated by cAMP, it is certain that many are. Neither is there much information on the specificity of protein kinase. It would seem that in most cases any protein kinase can phosphorylate any protein in spite of the molecular diversity of the kinase. Among the proteins that can be phosphory-lated are plasma membrane, microtubules, micro-somes, nucleic acid proteins, and histones. 

The growth requirement for EGF is a good example in this regard. EGF stimulates the growth of many different types of animal cells in culture. In order to initiate the growth response, EGF interacts with specific EGF receptors localized in the plasma membrane, activating a tyrosine-specific protein kinase, which is an intrinsic part of the receptor (Figure 12). As a consequence, specific proteins are phosphorylated at tyrosine residues, and some of these proteins (which are also... 

TBT and TFT are membrane-active molecules, and their mechanism of action appears to be strongly dependent on organotin(IV) lipophilicity. They function as ionophores and produce hemolysis, release Ca(II) from sarcoplasmic reticulum, alter phosphatodylseiine-induced histamine release, alter mitochondrial membrane permeability and perturb membrane enzymes. Organotin(IV) compounds have been shown to affect cell signaling they activate protein kinase and increase free arachidonic acid through the activation of phospholipase... 

Recent evidence indicates that the 5-HT transporter is subject to post-translational regulatory changes in much the same way as neurotransmitter receptors (Blakeley et al. 1998). Protein kinase A and protein kinase C (PKC), at least, are known to be involved in this process. Phosphorylation of the transporter by PKC reduces the Fmax for 5-HT uptake and leads to sequestration of the transporter into the cell, suggesting that this enzyme has a key role in its intracellular trafficking. Since this phosphorylation is reduced when substrates that are themselves transported across the membrane bind to the transporter (e.g. 5-HT and fi -amphetamine), it seems that the transport of 5-HT is itself linked with the phosphorylation process. Possibly, this process serves as a homeostatic mechanism which ensures that the supply of functional transporters matches the demand for transmitter uptake. By contrast, ligands that are not transported (e.g. cocaine and the selective serotonin reuptake inhibitors (SSRIs)) prevent the inhibition of phosphorylation by transported ligands. Thus, such inhibitors would reduce 5-HT uptake both by their direct inhibition of the transporter and by disinhibition of its phosphorylation (Ramamoorthy and Blakely 1999). 

ATP certainly fulfils the criteria for a NT. It is mostly synthesised by mitochondrial oxidative phosphorylation using glucose taken up by the nerve terminal. Much of that ATP is, of course, required to help maintain Na+/K+ ATPase activity and the resting membrane potential as well as a Ca +ATPase, protein kinases and the vesicular binding and release of various NTs. But that leaves some for release as a NT. This has been shown in many peripheral tissues and organs with sympathetic and parasympathetic innervation as well as in brain slices, synaptosomes and from in vivo studies with microdialysis and the cortical cup. There is also evidence that in sympathetically innervated tissue some extracellular ATP originates from the activated postsynaptic cell. While most of the released ATP comes from vesicles containing other NTs, some... 

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