The Role of Protein Kinase C and Protein Tyrosine Kinase in the Signal Transduction Pathway of stimulus Induced by Endotoxin in Peripheral Blood Monocyte

1997 ◽  
Vol 44 (2) ◽  
pp. 338
Author(s):  
Jae Yeol Kim ◽  
Jae Suk Park ◽  
Gwi Lae Lee ◽  
Chul Gyu Yoo ◽  
Young Whan Kim ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Peripheral Blood ◽  
Protein Tyrosine Kinase ◽  
Signal Transduction Pathway ◽  
Peripheral Blood Monocyte ◽  
Transduction Pathway ◽  
Kinase C

scholarly journals Lactosylceramide-enriched glycosphingolipid signaling domain mediates superoxide generation from human neutrophils

Blood ◽  
2002 ◽  
Vol 100 (4) ◽  
pp. 1454-1464 ◽  
Author(s):  
Kazuhisa Iwabuchi ◽  
Isao Nagaoka
Keyword(s):  
Signal Transduction ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Kinase Inhibitor ◽  
Signal Transduction Pathway ◽  
Transduction Pathway ◽  
Phosphatidylinositol 3 Kinase ◽  
Superoxide Generation ◽  
Kinase C ◽  
Signaling Domain

This study is focused on the functional significance of neutrophil lactosylceramide (LacCer)–enriched microdomains, which are involved in the initiation of a signal transduction pathway leading to superoxide generation. Treatment of neutrophils with anti-LacCer antibody, T5A7 or Huly-m13, induced superoxide generation from the cells, which was blocked by PP1, a Src kinase inhibitor; wortmannin, a phosphatidylinositol-3 kinase inhibitor; SB203580, a p38 mitogen-activated protein kinase (MAPK) inhibitor; and H7, an inhibitor for protein kinase C. When promyelocytic leukemia HL-60 cells were differentiated into neutrophilic lineage by dimethyl sulfoxide (DMSO) treatment, they acquired superoxide-generating activity but did not respond to anti-LacCer antibodies. Density gradient centrifugation revealed that LacCer and Lyn were recovered in detergent-insoluble membrane (DIM) of neutrophils and DMSO-treated HL-60 cells. However, immunoprecipitation experiments indicated that LacCer was associated with Lyn in neutrophils but not in DMSO-treated HL-60 cells. Interestingly, T5A7 induced the phosphorylation of Lyn in neutrophils but not in DMSO-treated HL-60 cells. Moreover, T5A7 induced the phosphorylation of p38 MAPK in neutrophils. T5A7-induced Lyn phosphorylation in neutrophil DIM fraction was significantly enhanced by cholesterol depletion or sequestration with methyl-β-cyclodextrin or nystatin. Collectively, these data suggest that neutrophils are characterized by the presence of cell surface LacCer-enriched glycosphingolipid signaling domain coupled with Lyn and that the ligand binding to LacCer induces the activation of Lyn, which may be suppressibly regulated by cholesterol, leading to superoxide generation through the phosphatidylinositol-3 kinase–, p38 MAPK–, and protein kinase C–dependent signal transduction pathway.

scholarly journals Role of type 1 and type 2A phosphatases in signal transduction of platelet-activating-factor-stimulated rabbit platelets

1994 ◽  
Vol 301 (2) ◽  
pp. 531-537 ◽  
Author(s):  
C T Murphy ◽  
J Westwick
Keyword(s):  
Signal Transduction ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Platelet Activating Factor ◽  
Signal Transduction Pathway ◽  
Calyculin A ◽  
Signal Molecule ◽  
Kinase C

Calyculin A, the potent inhibitor of type 1 (PP1) and type 2A (PP2A) phosphatases, has been employed in order to investigate the role of endogenously activated PP1/PP2A in the signal-transduction pathway of platelet-activating-factor (PAF)-stimulated platelets. Calyculin A alone caused an increase in protein phosphorylation in unstimulated platelets, with the detection of a number of newly phosphorylated proteins, whereas in PAF-stimulated platelets phosphorylation of the major substrates of protein kinase C and myosin light-chain kinase were no longer transient, but phosphorylation was sustained. PP1/PP2A appear to play a role in Ca2+ homoeostasis, as inhibition of PP1/PP2A caused an inhibition of Ca2+ mobilization and Ca2+ influx through the plasma membrane in PAF-stimulated platelets. The effect of calyculin A on Ca2+ mobilization correlated with the observed inhibition of the production of the signal molecule Ins(1,4,5)P3. The release reaction (which is a Ca(2+)-dependent event) was also inhibited by calyculin A. The results are discussed in relation to the possible role of protein kinase C in mediating the events leading to the effects observed with calyculin A.

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