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1.
A D Beyers C Hanekom A Rheeder A F Strachan M W Wooten A E Nel 《Journal of immunology (Baltimore, Md. : 1950)》1988,141(10):3463-3470
Protein kinase C (PKC) regulates numerous T cell functions and is present in abundance in normal human T cells and certain T cell lines. Although crude Triton X-100 soluble material obtained from T cell pellets contains minimal PKC activity, DEAE chromatography revealed that 12 to 37% of cellular PKC was membrane associated, probably due to removal of an inhibitor through column chromatography. As in other tissues, PKC from lymphoid tissue was phospholipid and Ca2+ dependent and diolein reduced the Ca2+ requirements for enzyme activity. Hydroxylapatite chromatography revealed that T cells possess two major peaks of PKC activity. Although, the enzyme in these peaks had similar m.w. and identical iso-electric mobility, the proteins differed with respect to their autophosphorylation sites and immunoreactivity toward an isoform specific antibody. Furthermore, differences in their activities in the presence of phospholipid, diolein, and limiting amounts of Ca2+ imply that these isoforms may be differentially activated. We discuss optimal conditions for activation of PKC and its isoforms for study of T lymphocyte cellular function. 相似文献
2.
Polymyxin B causes coordinate inhibition of phorbol ester-induced C-kinase activity and proliferation of B lymphocytes 总被引:5,自引:0,他引:5
A E Nel M W Wooten P J Goldschmidt-Clermont P J Miller H C Stevenson R M Galbraith 《Biochemical and biophysical research communications》1985,128(3):1364-1372
Lymphocytes were found to be rich in phospholipid/Ca2+-dependent (C-kinase) activity. Addition of polymyxin B (PMB) to in vitro assays of endogenous and exogenous phosphorylation resulted in profound inhibition of C-kinase activity. The phorbol ester 12-o-tetradecanoyl phorbol-13-acetate (TPA) directly activated C-kinase, leading to increased phosphorylation of the same substrates. TPA also stimulated proliferation of B cells as assessed by 3H-thymidine uptake, and PMB strongly inhibited this effect. This coordinate inhibition of TPA-induced phosphorylation and mitogenesis indicates that PMB is a potentially useful inhibitor of C-kinase activity, and that this enzyme may play an important role in mediating B cell responses. 相似文献
3.
M W Wooten 《Experimental cell research》1991,193(2):274-278
Heat shock treatment of rat embryo fibroblasts resulted in a 60% increase in cytosolic protein kinase C activity, in contrast to phorbol ester-induced translocation to the membrane. During reversal of the cells back to the normal temperature a decrease in cytosolic PKC activity was observed and paralleled by an increase in protamine kinase activity. Cell lysates prepared from heat shock-treated cells show a marked calcium/phospholipid-dependent phosphorylation of several endogenous PKC substrate proteins, while the 28-kDa stress protein was shown to be a PKC substrate. These cells express the TYPE III-alpha isoform of PKC and, thus, the alterations induced within cells exposed to hyperthermic treatment may reflect a functional significance with regard to the regulation of this specific isoform. 相似文献
4.
Michelle A. Arya Albert K. Tai Eric C. Wooten Christopher D. Parkin Elena Kudryavtseva Gordon S. Huggins 《PloS one》2013,8(8)
The loss of muscle mass in alcoholic myopathy may reflect alcohol inhibition of myogenic cell differentiation into myotubes. Here, using a high content imaging system we show that ethanol inhibits C2C12 myoblast differentiation by reducing myogenic fusion, creating smaller and less complex myotubes compared with controls. Ethanol administration during C2C12 differentiation reduced MyoD and myogenin expression, and microarray analysis identified ethanol activation of the Notch signaling pathway target genes Hes1 and Hey1. A reporter plasmid regulated by the Hes1 proximal promoter was activated by alcohol treatment in C2C12 cells. Treatment of differentiating C2C12 cells with a gamma secretase inhibitor (GSI) abrogated induction of Hes1. On a morphological level GSI treatment completely rescued myogenic fusion defects and partially restored other myotube parameters in response to alcohol. We conclude that alcohol inhibits C2C12 myoblast differentiation and the inhibition of myogenic fusion is mediated by Notch pathway activation. 相似文献
5.
6.
Keddie EM Higazi T Boakye D Merriweather A Wooten MC Unnasch TR 《Experimental parasitology》1999,93(4):198-206
West African populations of Onchocerca volvulus endemic to the rain forest and savanna bioclimes of West Africa differ in their ability to induce ocular disease in infected individuals. In recent years, both clinical- and animal-model-based studies have implicated particular parasite antigens in the development of ocular onchocerciasis. To test the hypothesis that the difference in pathogenic potential of blinding and nonblinding parasites might be reflected in qualitative differences in antigens that have been implicated in the development of ocular onchocerciasis, we compared the sequences of two parasite antigens implicated in the development of ocular disease in blinding- and nonblinding-strain parasites. The results demonstrated a high level of homogeneity between the parasite strains in these genes. The study was extended to include additional nuclear genes encoding antigens that are commonly recognized by individuals infected with O. volvulus and to the mitochondrial genome of the parasite. The results demonstrate a high degree of homogeneity in both the nuclear and the mitochondrial genomes among O. volvulus isolates collected from several different sites in Africa and in the Americas. This high degree of genetic homogeneity may reflect the passage of the parasite through a recent genetic bottleneck. 相似文献
7.
The Class II histone deacetylase, HDAC6, has been shown to be involved in cell motility, aggresome formation and mitochondria transport. HDAC6 deacetylase activity regulates α-tubulin acetylation levels and thus plays a critical role in these processes. In turn, HDAC6 activity can be regulated by interaction with various proteins including multiple kinases. Kinase mediated phosphorylation of HDAC6 can lead to either increased or reduced activity. Our previous research has shown that sequestosome1/p62 (SQSTM1/p62) interacts with HDAC6 and regulates its activity. As SQSTM1/p62 is a scaffolding protein known to interact directly with the zeta isoform of Protein Kinase C (PKCζ), we sought to examine if HDAC6 could be a substrate for PKCζ phosphorylation and if so, how its activity might be regulated. Our data demonstrate that HDAC6 is not only present in a protein complex with PKCζ but can also be phosphorylated by PKCζ. We also show that specific phosphorylation of HDAC6 by PKCζ increases HDAC6 deacetylase activity resulting in reduced acetylated tubulin levels. Our findings provide novel insight into the molecular mechanism by which HDAC6, PKCζ and SQSTM1/p62 function together in protein aggregate clearance. These results also highlight a new research direction which may prove fruitful for understanding the underlying cause of several neurodegenerative diseases. 相似文献
8.
To obtain more efficient operation of a COBE Model 2997 clinical cell separator using either a Single Stage II (SS II) or a Dual Stage separation chamber, modifications were made to allow complete computer control. Product cell density was detected using an optical sensor and controlled by automatic feedback through a microcomputer interface. Control was accomplished by automatically adjusting the red blood cell (RBC) and plasma product flow rates using a proportional-integral (PI) algorithm. Results show that, using either chamber, the product cell density can be maintained at a preselected value for extended periods of time without operator intervention. This system allowed investigation of optimal operating regions for plateletpheresis and leukapheresis procedures. The effects of centrifuge rpm and controller set point on centrifuge operation were investigated using a second order factorial experimental design. Theoretical significance of model parameters was assessed with the aid of a hindered settling model and simple reasoning about the interface position relative to the collection port. The results suggest that, in either chamber, the optimum operating region for plateletpheresis procedures occurs at moderate controller set points and high centrifuge rpm. The resultant operating efficiency and product purity values are approximately 63 percent and 0.65 respectively in the SS II chamber and approximately 70 percent and 0.70 respectively in the Dual Chamber. In the SS II, the optimum operating region for leukapheresis procedures occurred at high controller set point values for any centrifuge rpm above 1200 with an operating efficiency near 100 percent. However, in the Dual Chamber, the optimum operating region for leukapheresis procedures occurred at high controller set points and high centrifuge rpm's, again providing an operating efficiency near 100 percent. 相似文献
9.
Translocation of phospholipid/Ca2+-dependent protein kinase in B-lymphocytes activated by phorbol ester or cross-linking of membrane immunoglobulin. 总被引:6,自引:0,他引:6
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A E Nel M W Wooten G E Landreth P J Goldschmidt-Clermont H C Stevenson P J Miller R M Galbraith 《The Biochemical journal》1986,233(1):145-149
Treatment of hepatocytes with islet activating protein (pertussis toxin) from Bordetella pertussis blocked the ability of insulin to inhibit adenylate cyclase activity both in broken plasma membranes and in intact hepatocytes. Such treatment of intact hepatocytes with pertussis toxin did not prevent insulin from activating the peripheral plasma membrane cyclic AMP phosphodiesterase although it did inhibit the ability of insulin to activate the 'dense-vesicle' cyclic AMP phosphodiesterase. The ability of glucagon pretreatment of hepatocytes to block insulin's activation of the plasma membrane cyclic AMP phosphodiesterase was abolished in pertussis toxin-treated hepatocytes. It is suggested that the ability of insulin to manipulate cyclic AMP concentrations by inhibiting adenylate cyclase and activating the plasma membrane and 'dense-vesicle' cyclic AMP phosphodiesterases involves interactions with the guanine nucleotide regulatory protein system occurring in liver plasma membranes. 相似文献
10.
TRAF6-mediated ubiquitination regulates nuclear translocation of NRIF, the p75 receptor interactor 总被引:1,自引:0,他引:1
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TRAF6 is an E3 ubiquitin ligase that mediates signaling from members of the tumor necrosis factor and Toll-like receptor superfamilies, including the p75 neurotrophin receptor. Recently, TRAF6 was shown to bind to another p75 cytoplasmic interactor, NRIF, and promote its nuclear localization. Here, we demonstrate that NRIF is a substrate for TRAF6-mediated K63 polyubiquitination and that this modification is necessary for its nuclear translocation. Activation of p75 resulted in NRIF polyubiquitination, association with TRAF6 and nuclear localization. NRIF was polyubiquitinated by TRAF6 in vitro and in cultured cells, and this was abrogated by mutation of K19 in the amino-terminus of NRIF. The K19R mutant NRIF displayed reduced TRAF6 association and neurotrophin-dependent nuclear localization. In neurons from traf6-/- mice, NRIF failed to enter the nucleus in response to p75 activation, and polyubiquitination and nuclear localization were attenuated in traf6-/- brain. Finally, unlike wild-type NRIF, the K19R NRIF failed to reconstitute p75-mediated apoptosis in nrif-/- neurons. These results reveal a unique mechanism of p75 signaling and a novel role for K63-linked ubiquitin chains. 相似文献