Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of urokinase-type plasminogen activator (uPA) and its receptor (uPAR/CD87) in cell migration and invasion is well substantiated. Recently, uPA has been shown to be essential in cell migration, since uPA-/- mice are greatly impaired in inflammatory cell recruitment. We have shown previously that the uPA-induced chemotaxis requires interaction with and modification of uPAR/CD87, which is the true chemoattracting molecule acting through an unidentified cell surface component which mediates this cell surface chemokine activity. By expressing and testing several uPAR/CD87 variants, we have located and functionally characterized a potent uPAR/CD87 epitope that mimics the effects of the uPA-uPAR interaction. The chemotactic activity lies in the region linking domains 1 and 2, the only protease-sensitive region of uPAR/CD87, efficiently cleaved by uPA at physiological concentrations. Synthetic peptides carrying this epitope promote chemotaxis and activate p56/p59(hck) tyrosine kinase. Both chemotaxis and kinase activation are pertussis toxin sensitive, involving a Gi/o protein in the pathway.
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PMID:A urokinase-sensitive region of the human urokinase receptor is responsible for its chemotactic activity. 940 57

The chemokine RANTES (regulated on activation normal T cell expressed and secreted) and its cognate receptor CC chemokine receptor 5 (CCR5) have been implicated in regulating immune cell function. Previously we reported that in T cells, RANTES activation of CCR5 results in Stat1 and Stat3 phosphorylation-activation, leading to Stat1:1 and Stat1:3 dimers that exhibit DNA binding activity and the transcriptional induction of a Stat-inducible gene, c-fos. Given that RANTES and CCR5 have been implicated in T cell activation, we have studied RANTES-induced signaling events in a CCR5-expressing T cell line, PM1. RANTES treatment of PM1 T cells results in the rapid phosphorylation-activation of CCR5, Jak2, and Jak3. RANTES-inducible Jak phosphorylation is insensitive to pertussis toxin inhibition, indicating that RANTES-CCR5-mediated tyrosine phosphorylation events are not coupled directly to Galpha(i) protein-mediated events. In addition to Jaks, several other proteins are rapidly phosphorylated on tyrosine residues in a RANTES-dependent manner, including the Src kinase p56(lck), which associates with Jak3. Additionally our data confirm that the amino-terminally modified RANTES proteins, aminooxypentane-RANTES and Met-RANTES, are agonists for CCR5 and induce early tyrosine phosphorylation events that are indistinguishable from those inducible by RANTES with similar kinetics. Our data also demonstrate that RANTES activates the p38 mitogen-activated protein (MAP) kinase pathway. This is evidenced by the rapid RANTES-dependent phosphorylation and activation of p38 MAP kinase as well as the activation of the downstream effector of p38, MAP kinase-activated protein (MAPKAP) kinase-2. Pharmacological inhibition of RANTES-dependent p38 MAP kinase activation blocks MAPKAP kinase-2 activity. Thus, activation of Jak kinases and p38 MAP kinase by RANTES regulates the engagement of multiple signaling pathways.
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PMID:Rantes activates Jak2 and Jak3 to regulate engagement of multiple signaling pathways in T cells. 1127 38

Viruses have evolved a number of strategies to gain entry and replicate in host target cells that, for human immunodeficiency virus (HIV) and the poxvirus, myxoma virus, involve appropriating chemokine receptors. In this report we demonstrate that activation of multiple intracellular tyrosine phosphorylation events rapidly ensues following virus adsorption to NIH 3T3.CD4.CCR5 cells and affects the ultimate level of myxoma virus replication. UV-inactivated myxoma virus induces the rapid phosphorylation of CCR5 on tyrosine residues, the association of CCR5 with Jaks and p56(lck), and their phosphorylation-activation within minutes of virus adsorption. Additionally, we provide evidence for myxoma virus-inducible signal transducers and activators of transcription (Stat) and insulin receptor substrate (IRS) activation. In contrast to CCR5 activation effected by HIV Env protein, these myxoma virus-inducible phosphorylation events are not sensitive to pertussis toxin treatment. Moreover, in cells that are non-permissive for myxoma virus infection, we provide evidence that myxoma virus fails to invoke this tyrosine phosphorylation cascade. Consistent with the observation that infection of CCR5-expressing cells is blocked by herbimycin A and the Jak 2 inhibitor, tyrophostin AG490, we infer that viral infectivity may be dependent on non-G-protein-coupled signal transduction pathways triggered by the infecting myxoma virus particle. This provides a novel post-binding mechanism by which viruses can co-opt a cellular receptor to permit productive virus infection.
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PMID:Poxvirus infection rapidly activates tyrosine kinase signal transduction. 1159 16

Lysophospholipids, particularly lysophosphatidylcholine (lyso-PC), have been implicated in modulating T cell functions at the sites of inflammation and atherosclerosis. Although the chemotactic and immunomodulatory effects are well documented, the exact signaling pathway of lyso-PC action is poorly defined. In this work, we studied the earliest biochemical events in T cells triggered by lyso-PC. A marked and immediate tyrosine phosphorylation was induced in the leukemic T cell line, Jurkat. Phosphorylation of cellular substrates included src family kinase, p56(lck) and syk family kinase, ZAP70. The lyso-PC induced tyrosine phosphorylation was largely dependent on the presence of functional p56(lck). Tyrosine phosphorylation was followed by the elevation of intracellular Ca(2+) concentration. The magnitude of the mobilization of the intracellular Ca(2+) was similar in the absence of the p56(lck) activity in JCaM1.6 cells as in Jurkat cells, however, it was slightly but reproducibly delayed compared to that in the wild type cells. Inhibition of the Ser/Thr kinases and tyrosine kinases with staurosporine and genistein, respectively, decreased the rise in the intracellular Ca(2+) content. Moreover, pertussis toxin completely blocked the Ca(2+) signal supporting the role of the G-protein coupled LPC receptor in this event.
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PMID:Lysophosphatidylcholine is a regulator of tyrosine kinase activity and intracellular Ca(2+) level in Jurkat T cell line. 1475 65