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 investi gated the signaling mechanisms responsible for PTX-induced differentiated U 937 cell adhesion. PTX-induced myelomonocytic cell adhesion was blocked by genistein or tyrphostin-47 (two protein tyrosine kinase inhibitors), LY2940 92 (a phosphatidylinositol 3-kinase (PI3K) inhibitor), or PD098059 (a mitog en-activated protein kinase (MAPK)/extracellular signal-regulated kinase (E RK) kinase (MEK) inhibitor). PTX induced a rapid tyrosine phosphorylation o f several discrete cytoplasmic proteins, which could be inhibited by genist ein or tyrphostin 47, In addition, PTX induced phosphorylation of Akt and o f ERK2, which could be completely blocked by LY294002 and PD098059, respect ively, 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 cascad e, including the downstream PI3K and ERK/MAPK pathways, in myelomonocytic c ells to induce cell adhesion to serum. (C) 2001 Academic Press.