Transforming growth factor-β-mediated mast cell migration depends on mitogen-activated protein kinase activity

N Olsson, E Piek, M Sundström, P ten Dijke, G Nilsson - Cellular signalling, 2001 - Elsevier
N Olsson, E Piek, M Sundström, P ten Dijke, G Nilsson
Cellular signalling, 2001Elsevier
Transforming growth factor-β (TGF-β) isoforms regulate numerous cellular functions through
binding to receptors with intrinsic serine/threonine kinase activity that transduce the
intracellular signals via activation of Smad proteins. In this study, we examined the signalling
pathways involved in TGF-β1-mediated growth inhibition and migration in a human mast cell
line, HMC-1. TGF-β1 evoked optimal migration at 40 fM, whereas maximal growth inhibition
was obtained at 400 pM. Protein tyrosine kinase inhibitors completely inhibited TGF-β1 …
Transforming growth factor-β (TGF-β) isoforms regulate numerous cellular functions through binding to receptors with intrinsic serine/threonine kinase activity that transduce the intracellular signals via activation of Smad proteins. In this study, we examined the signalling pathways involved in TGF-β1-mediated growth inhibition and migration in a human mast cell line, HMC-1. TGF-β1 evoked optimal migration at 40 fM, whereas maximal growth inhibition was obtained at 400 pM. Protein tyrosine kinase inhibitors completely inhibited TGF-β1-mediated migration, without affecting the antimitogenic response. Smad2 was phosphorylated upon TGF-β1 treatment, both in the absence and presence of genistein. The mitogen-induced extracellular kinase (MEK) inhibitor, PD98059, blocked the migratory response without affecting growth inhibition. In contrast, the p38 MAP kinase inhibitor, SB203580, had no significant effect on either migration or growth inhibition. These results indicate that different signalling pathways mediate TGF-β1-induced migration and growth inhibition in HMC-1 cells, where the migration involves MEK activity.
Elsevier