TGF-beta receptors (T beta Rs) are serine/threonine kinase receptors that bind to TGF-beta and propagate intracellular signaling through Smad proteins. T beta Rs are repressed in some human cancers and expressed at high levels in several fibrotic diseases. We demonstrated that epidermal growth factor (EGF) up-regulates type 11 TGF-beta receptor (T beta RII) expression in human dermal fibroblasts. EGF-mediated induction of T beta RII expression was inhibited by the treatment of fibroblasts with a specific p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580, whereas MEK inhibitor PD98059 did not block the up-regulation of T beta RII by EGF. EGF induced the T beta RII promoter activity, and this induction was significantly blocked by SB203580, but not by PD98059. The overexpression of the dominant negative form of p38 alpha or p38 beta significantly reduced the induction of T beta RII promoter activity by EGF. These results indicate that the EGF-mediated induction of T beta RII expression involves the p38 MAPK signaling pathway. The EGF-mediated induction of T beta RII expression may participate in a synergistic interplay between EGF and TGF-beta signaling pathway. (c) 2006 Elsevier Inc. All rights reserved.