The T cell receptor-mediated phosphorylation of Pyk2 tyrosines 402 and 580 occurs via a distinct mechanism than other receptor systems.
The tyrosine kinase Pyk2 is vital for integrating receptor-mediated signals controlling adhesion and motility in neuronal, epithelial, and hematopoietic cell types. In T cells, the stimulation of the TCR and costimulatory, chemokine, cytokine, and integrin receptors leads to the phosphorylation of Pyk2 and the induction of its catalytic activity. However, our understanding of the mechanism of the TCR-induced, site-specific phosphorylation of this kinase is incomplete and contradictory. To address this issue, the role of individual signaling pathways in the phosphorylation of Pyk2 tyrosines 402 and 580 upon TCR activation was assessed in human T cells. In contrast to other receptor systems, the TCR-induced phosphorylation of Pyk2 tyrosines 402 and 580 was dependent on the Src family kinases, Fyn or Lck. Interestingly, the TCR-mediated phosphorylation of Pyk2 tyrosines 402 and 580 did not require Ca(2+) influx, ZAP-70 activation, actin cytoskeleton rearrangement, or PI3K function. These observations are different than other receptor systems, which require the induction of one or more of these pathways. Together, these data have defined more fully the mechanism for the TCR-induced phosphorylation of specific sites on Pyk2, suggesting that the TCR has a distinct pathway for the activation of Pyk2 compared with other receptor systems.
Collins
Michaela
M
Department of Microbiology, Carver College of Medicine, University of Iowa, 2210 MERF, Iowa City, IA 52242, USA.
Tremblay
Mikaela
M
Chapman
Nicole
N
Curtiss
Miranda
M
Rothman
Paul B
PB
Houtman
Jon C D
JC
D002118:Calcium / Q000276:immunology / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D004789:Enzyme Activation / Q000276:immunology; D051418:Focal Adhesion Kinase 2 / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation / Q000276:immunology; D051076:Proto-Oncogene Proteins c-fyn / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D014443:Tyrosine / Q000276:immunology / Q000378:metabolism*; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000276:immunology / Q000378:metabolism
D011948:Receptors, Antigen, T-Cell; D014443:Tyrosine; C494957:FYN protein, human; D051418:Focal Adhesion Kinase 2; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); C103547:PTK2B protein, human; D051076:Proto-Oncogene Proteins c-fyn; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D002118:Calcium