Signalling pathways induced by protease-activated receptors and integrins in T cells.
Recent characterization of the thrombin receptor indicates that it plays a role in T-cell signalling pathways. However, little is known regarding the signalling events following stimulation of additional members of the protease-activated receptor (PAR) family, i.e. PAR2 and PAR3. Most of the postligand cascades are largely unknown. Here, we illustrate that in Jurkat T-leukaemic cells, activation of PAR1, PAR2 and PAR3 induce tyrosine phosphorylation of Vav1. This response was impaired in Jurkat T cells deficient in p56lck (JCaM1.6). Activation of PARs also led to an increase in tyrosine phosphorylation of ZAP-70 and SLP-76, two key proteins in T-cell receptor (TCR) signalling. We also demonstrated that p56lck is meaningful for integrin signalling. Thus, JCaM1.6 cells exhibited a marked reduction in their adherence to fibronectin-coated plates, as compared to the level of adherence of Jurkat T cells. While the phosphorylation of Vav1 in T cells is augmented following adhesion, no additional increase was noted following treatment of the adhered cells with PARs. Altogether, we have identified key components in the postligand-signalling cascade of PARs and integrins. Furthermore, we have identified Lck as a critical and possibly upstream component of PAR-induced Vav1 phosphorylation, as well as integrin activation, in Jurkat T cells.
Bar-Shavit
Rachel
R
Department of Oncology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Maoz
Miriam
M
Yongjun
Yin
Y
Groysman
Maya
M
Dekel
Idit
I
Katzav
Shulamit
S
D001345:Autoradiography; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D016023:Integrins / Q000502:physiology*; D008163:Luminescent Measurements; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000502:physiology; D010766:Phosphorylation; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology*; D014443:Tyrosine / Q000502:physiology; D014667:Vasopressins / Q000502:physiology
D016023:Integrins; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; D014667:Vasopressins; D014443:Tyrosine; C080853:vasopressinase-altered vasopressin; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)