Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously shown that apoptosis induced in thymocytes by dexamethasone or teniposide (VM-26) could be inhibited by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7) and sangivamycin, both relatively specific inhibitors for protein kinase C, but not by N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA1004), a more specific inhibitor for cAMP-dependent protein kinases. Apoptosis in this model system was not blocked by EGTA and no increase in cytosolic Ca2+ was observed during apoptosis induced by either dexamethasone or VM-26, suggesting that this kinase was Ca2+-independent. In the present study, we demonstrate that addition of 10 microM sangivamycin to thymocyte cultures up to 2 h after addition of either inducer resulted in virtually complete inhibition of apoptosis. Addition of 10 microM sangivamycin at 3 or 4 h after addition of inducer resulted in partial inhibition of apoptosis. Computerized image analysis of two-dimensional PAGE analyses of whole-cell lysates demonstrated that treatment of mouse thymocytes with VM-26 resulted in a limited number of de novo phosphorylation events within 1 h of treatment. The most prominent phosphorylation events associated with VM-26-induced apoptosis were that two intracellular protein species (Protein 1: m.w. = 22.9 kDa, pI, 5.11; and Protein 2: m.w. = 22.9 kDa, pI, 4.98). Similar phosphorylation events were seen in cells treated with dexamethasone. Finally, Western blot analysis suggests that de novo protein phosphorylation induced by VM-26 is on serine/threonine residues. These results provide further evidence that the mechanism of VM-26-induced apoptosis of murine thymocytes involves the action of one or more serine/threonine kinases.
 ...
PMID:Protein phosphorylation associated with epipodophyllotoxin-induced apoptosis of lymphoid cells: role of a serine/threonine protein kinase. 978 13

Presynaptic exocytosis is the mechanism commonly believed to release transmitters by diffusion through a pore opening during vesicular membrane fusion with the plasmalemma, but evidence suggesting that exocytosis and transmitter release are two separate steps of synaptic transmission is accumulating. Vesicular glycoconjugates such as Synaptic Vesicle Protein 2 (SV2) proteoglycans and gangliosides retain transmitters in a nondiffusible form and are transported to the synaptic cleft where they contribute forming a dense synaptomatrix. Transmitters are permanently present in synaptic clefts and readily releasable transmitter is easily accessible from the outer side of the presynaptic membrane suggesting that synaptomatrix glycoconjugates prevent immediate release after PKC-dependent exocytosis. The calcium sensor synaptotagmin is also present at the presynaptic plasma membrane and binds SV2 suggesting a direct coupling between the calcium transient and transmitter release from the synaptomatrix. A quantitative coupling of the cytosolic calcic transient to transmitter release from the synaptomatrix explains better complexity and plasticity of miniature postsynaptic signals hitherto difficult to account for in exocytic terms. This alternative representation of synaptic transmission in which the same components of the synaptomatrix support adhesion and signaling functions may cast new lights on synaptic diseases such as Alzheimer's disease.
 ...
PMID:SV2 frustrating exocytosis at the semi-diffusor synapse. 1914 Jan 66