Pertussis toxin activates tyrosine kinase signaling cascade in myelomonocytic cells: a mechanism for cell adhesion.
Pertussis toxin (PTX) has recently been shown to specifically bind to CD14 to promote myelomonocytic cell adhesion to serum. The present study investigated the signaling mechanisms responsible for PTX-induced differentiated U937 cell adhesion. PTX-induced myelomonocytic cell adhesion was blocked by genistein or tyrphostin-47 (two protein tyrosine kinase inhibitors), LY294002 (a phosphatidylinositol 3-kinase (PI3K) inhibitor), or PD098059 (a mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor). PTX induced a rapid tyrosine phosphorylation of several discrete cytoplasmic proteins, which could be inhibited by genistein or tyrphostin 47. In addition, PTX induced phosphorylation of Akt and of ERK2, which could be completely blocked by LY294002 and PD098059, respectively, and by genistein or tyrphostin 47 as well. All of these PTX-induced signaling events could be reproduced using purified PTX B-oligomer (PTX-B) alone. Our data show that PTX can activate tyrosine kinase signaling cascade, including the downstream PI3K and ERK/MAPK pathways, in myelomonocytic cells to induce cell adhesion to serum.
Li
H
H
Department of Pharmacology, National University of Singapore, 117597, Singapore
Wong
W S
WS
D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002867:Chromones / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D018950:Lipopolysaccharide Receptors / Q000187:drug effects / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D037342:Pertussis Toxin; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D020032:Tyrphostins / Q000494:pharmacology; D020298:U937 Cells; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D002867:Chromones; D004791:Enzyme Inhibitors; D005419:Flavonoids; D018950:Lipopolysaccharide Receptors; D009025:Morpholines; D016212:Transforming Growth Factor beta; D020032:Tyrphostins; D010566:Virulence Factors, Bordetella; C060152:tyrphostin 47; D019000:Phosphotyrosine; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019833:Genistein; D037342:Pertussis Toxin; D011505:Protein-Tyrosine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D004121:Dimethyl Sulfoxide