scholarly journals Progesterone and the zona pellucida activate different transducing pathways in the sequence of events leading to diacylglycerol generation during mouse sperm acrosomal exocytosis

1996 ◽  
Vol 320 (3) ◽  
pp. 1017-1023 ◽  
Author(s):  
Tetsuma MURASE ◽  
Eduardo R. S. ROLDAN
Keyword(s):  
Tyrosine Kinase ◽  
G Protein ◽  
Pertussis Toxin ◽  
Zona Pellucida ◽  
Protein Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
Dependent Manner ◽  
Protein Tyrosine ◽  
Sequence Of Events ◽  
Acrosomal Exocytosis

We tested the involvement of protein tyrosine kinase and G-protein transducing pathways in the formation of diacylglycerol (DAG) during exocytosis in mouse spermatozoa. In capacitated spermatozoa, stimulation with solubilized zona pellucida (ZP) or progesterone led to the formation of DAG and to exocytosis of the acrosomal granule. Stimulation of DAG formation and exocytosis by ZP were inhibited in a concentration-dependent fashion by pre-exposure to tyrphostin A48, a protein tyrosine kinase inhibitor. These ZP-induced responses were also reduced in a concentration-dependent manner by prior incubation with pertussis toxin, a G-protein (Gi class) inhibitor. On the other hand, generation of DAG and exocytosis triggered by progesterone were inhibited if spermatozoa were preincubated with different concentrations of tyrphostin A48, but were not affected by pre-exposure to pertussis toxin. Progesterone acts on at least two novel surface receptors, one being a γ-aminobutyric acid (GABA) type A (GABAA)-like receptor. Transducing mechanisms coupled to this receptor were tested directly by stimulating spermatozoa with GABA. Treatment of capacitated spermatozoa with GABA resulted in DAG formation and exocytosis. These responses were not seen when cells were preincubated with tyrphostin A48. Pertussis toxin, however, did not affect the generation of DAG and exocytosis triggered by GABA, in agreement with results obtained using progesterone. Taken together, these results indicate that DAG formation during acrosomal exocytosis is differentially regulated by transducing pathways activated by oocyte-associated agonists.

Protein-tyrosine Kinase p72 syk Is Activated by Platelet Activating Factor in Platelets

1994 ◽  
Vol 72 (06) ◽  
pp. 937-941 ◽  
Author(s):  
Karim Rezaul ◽  
Shigeru Yanagi ◽  
Kiyonao Sada ◽  
Takanobu Taniguchi ◽  
Hirohei Yamamura
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Phosphorylation ◽  
Protein Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
Critical Role ◽  
Platelet Activating Factor ◽  
Kinase Assay ◽  
Potential Candidate ◽  
Protein Tyrosine ◽  
Induced Aggregation

SummaryIt has been demonstrated that activation of platelets by platelet-activating factor (PAF) results in a dramatic increase in tyrosine phosphorylation of several cellular proteins. We report here that p72 syk is a potential candidate for the protein-tyrosine phosphorylation following PAF stimulation in porcine platelets. Immunoprecipitation kinase assay revealed that PAF stimulation resulted in a rapid activation of p72 syk which peaked at 10 s. The level of activation was found to be dose dependent and could be completely inhibited by the PAF receptor antagonist, CV3988. Phosphorylation at the tyrosine residues of p72 syk coincided with activation of yllsyk. Pretreatment of platelets with aspirin and apyrase did not affect PAF induced activation of p72 syk .Furthermore, genistein, a potent protein-tyrosine-kinase inhibitor, diminished PAF-induced p72 syk activation and Ca2+ mobilization as well as platelet aggregation. These results suggest that p72 syk may play a critical role in PAF-induced aggregation, possibly through regulation of Ca2+ mobilization.

Cell surface beta-1,4-galactosyltransferase-I activates G protein-dependent exocytotic signaling

Development ◽  
2001 ◽  
Vol 128 (5) ◽  
pp. 645-654
Author(s):  
X. Shi ◽  
S. Amindari ◽  
K. Paruchuru ◽  
D. Skalla ◽  
H. Burkin ◽  
...  
Keyword(s):  
G Protein ◽  
G Proteins ◽  
Pertussis Toxin ◽  
Zona Pellucida ◽  
Acrosome Reaction ◽  
Cytoplasmic Domain ◽  
Protein Activation ◽  
Acrosomal Exocytosis ◽  
G Protein Activation ◽  
Galactosyltransferase I

ZP3 is a protein in the mammalian egg coat (zona pellucida) that binds sperm and stimulates acrosomal exocytosis, enabling sperm to penetrate the zona pellucida. The nature of the ZP3 receptor/s on sperm is a matter of considerable debate, but most evidence suggests that ZP3 binds to beta-1,4-galactosyltransferase-I (GalTase) on the sperm surface. It has been suggested that ZP3 induces the acrosome reaction by crosslinking GalTase, activating a heterotrimeric G protein. In this regard, acrosomal exocytosis is sensitive to pertussis toxin and the GalTase cytoplasmic domain can precipitate G(i) from sperm lysates. Sperm from mice that overexpress GalTase bind more soluble ZP3 and show accelerated G protein activation, whereas sperm from mice with a targeted deletion in GalTase have markedly less ability to bind soluble ZP3, undergo the ZP3-induced acrosome reaction, and penetrate the zona pellucida. We have examined the ability of GalTase to function as a ZP3 receptor and to activate heterotrimeric G proteins using Xenopus laevis oocytes as a heterologous expression system. Oocytes that express GalTase bound ZP3 but did not bind other zona pellucida glycoproteins. After oocyte maturation, ZP3 or GalTase antibodies were able to trigger cortical granule exocytosis and activation of GalTase-expressing eggs. Pertussis toxin inhibited GalTase-induced egg activation. Consistent with G protein activation, both ZP3 and anti-GalTase antibodies increased GTP-gamma[(35)S] binding as well as GTPase activity in membranes from eggs expressing GalTase. Finally, mutagenesis of a putative G protein activation motif within the GalTase cytoplasmic domain eliminated G protein activation in response to ZP3 or anti-GalTase antibodies. These results demonstrate directly that GalTase functions as a ZP3 receptor and following aggregation, is capable of activating pertussis toxin-sensitive G proteins leading to exocytosis.

Impact of treatment with a Protein Tyrosine Kinase Inhibitor (Genistein) on acute and chronic experimental Schistosoma mansoni infection

2018 ◽  
Vol 185 ◽  
pp. 115-123 ◽  
Author(s):  
Maysa Mohamed Kamel Sobhy ◽  
Soheir Sayed Mahmoud ◽  
Shaimaa Helmy El-Sayed ◽  
Enas Mohamed Ali Rizk ◽  
Amira Raafat ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Schistosoma Mansoni ◽  
Tyrosine Kinase Inhibitor ◽  
Protein Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
Protein Tyrosine ◽  
Protein Tyrosine Kinase Inhibitor

Emodin, a Protein Tyrosine Kinase Inhibitor from Polygonum cuspidatum

1992 ◽  
Vol 55 (5) ◽  
pp. 696-698 ◽  
Author(s):  
Hiranthi Jayasuriya ◽  
Nuphavan M. Koonchanok ◽  
Robert L. Geahlen ◽  
Jerry L. McLaughlin ◽  
Ching-Jer Chang
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Protein Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
Polygonum Cuspidatum ◽  
Protein Tyrosine ◽  
Protein Tyrosine Kinase Inhibitor

scholarly journals IL-1α Stimulates Cathepsin K Expression in Osteoclasts via the Tyrosine Kinase-NF-κB Pathway

2004 ◽  
Vol 83 (10) ◽  
pp. 791-796 ◽  
Author(s):  
S. Kamolmatyakul ◽  
W. Chen ◽  
S. Yang ◽  
Y. Abe ◽  
R. Moroi ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
Protein A ◽  
Cathepsin K ◽  
Underlying Mechanism ◽  
Transcriptional Level ◽  
Pyrrolidine Dithiocarbamate ◽  
Dependent Manner ◽  
Powerful Activator

Interleukin-1α (IL-1α) is a powerful activator of osteoclast cells. However, the underlying mechanism for this activation is unknown. In this study, we reveal that IL-1α up-regulates the expression of cathepsin K protein, a key protease in bone resorption, by five-fold. Northern blot analysis and promoter analysis show that this induction occurs at the transcriptional level, in a dose-responsive and time-dependent manner. No increase in expression occurs in the presence of either pyrrolidine dithiocarbamate (PDTC), a selective inhibitor of NF-κB, or Genistein, a protein tyrosine kinase inhibitor, suggesting that IL-1α up-regulation may be via the tyrosine kinase-NF-κB pathway to regulate cathepsin K expression. Antisense oligonucleotides to p65, but not the p50 subunit of NF-κB, suppress the IL-1α-induced expression of cathepsin K. We therefore conclude that IL-1α up-regulates cathepsin K gene expression at the transcription level, and this regulation may be via the tyrosine-kinase-NF-κB pathway.

scholarly journals The protein tyrosine kinase inhibitor genistein suppresses hypoxia-induced atrial natriuretic peptide secretion mediated by the PI3K/Akt-HIF-1α pathway in isolated beating rat atria

2021 ◽  
pp. 1-7
Author(s):  
Qiu-li Zhang ◽  
Ping Li ◽  
Lan Hong ◽  
Rui-zhuang Li ◽  
Jia-qi Wang ◽  
...  
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Tyrosine Kinase ◽  
Natriuretic Peptide ◽  
Protein Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
Acute Hypoxia ◽  
Hypoxia Inducible Factor ◽  
Protein Tyrosine ◽  
Downstream Signaling ◽  
Atrial Natriuretic

Genistein, an isoflavonoid that can inhibit protein tyrosine kinase (PTK) phosphorylation, has been shown to play pivotal roles in the signal transduction pathways of hypoxic disorders. In this study, we established a rat model of isolated beating atrium and investigated the regulator role of genistein and its downstream signaling pathways in acute hypoxia-induced atrial natriuretic peptide (ANP) secretion. Radioimmunoassay was used to detect the ANP content in the atrial perfusates. Western blot analysis was used to determine the protein level of hypoxia-inducible factor 1α (HIF-1α), and GATA4 in the atrial tissue. The results showed that acute hypoxia substantially promoted ANP secretion, whereas this effect was partly attenuated by the PTKs inhibitor genistein (3 μM). By Western blotting analysis, we found that hypoxia-induced increase in phosphorylation of Akt and transcriptional factors, including HIF-1α, were also reversed by genistein. The perfused HIF-1α inhibitors rotenone (0.5 μM) or CAY10585 (10 μM) plus genistein significantly abolished the enhanced ANP section induced by hypoxia. Additionally, the perfused PI3K/Akt agonist insulin-like growth factor 1 (30 μM) also abolished ANP secretion induced by genistein and inhibited expression of HIF-1α. In summary, our data suggested that acute hypoxia markedly increased ANP secretion by PTKs through the phosphoinositide-3 kinase (PI3K)/HIF-1α dependent pathway.

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