Signaling Pathway of TGF- . Signaling Pathway of TGF-
TGF- regulates growth and proliferation of cells, blocking the growth of many different cell types. The TGF- receptor includes Type I and Type II subunits that are serine-threonine kinases that signal through the SMAD family of proteins. Binding of transforming growth factor ß (TGF-) to its cell surface receptor Type II leads to the phosphorylation of the Type I receptor by Type II. The Type I receptor is then able to phosphorylate and activate the Smad2 protein. Smad2, in combination with Smad4, is translocated to the nucleus where the activated Smad complex recruits other transcription factors (TF) that together activate the expression of target genes that mediate the biological effects of TGF-. Some of the activated target genes stimulate tumorigenesis, while others suppress tumorigenesis.
Kawabata, M., and Miyazono, K., Signal transduction of the TGF- superfamily by Smad proteins. J. Biochem. (Tokyo), 125, 9-16 (1999).
Wrana, J.L., TGF- receptors and signalling mechanisms. Miner. Electrolyte Metab., 24, 120-130 (1998).
Markowitz, S.D., and Roberts, A.B., Tumor suppressor activity of the TGF- pathway in human cancers. Cytokine Growth Factor Rev., 7, 93-102 (1996).