Transforming growth factor beta (TGF-beta) is an important regulator of apoptosis in some cell types, but the underlying molecular mechanisms are largely unknown. TGF-beta signals through type I and type II receptors and downstream effector proteins, termed Smads. TGF-beta induces the phosphorylation of Smad2 and Smad3 (receptor-activated Smads) which associate with Smad4 and translocate to the...

Airway remodelling is characterized by the thickening and reorganization of the airways seen in mustard lung patients. Mustard lung is the general description for the chronic obstructive pulmonary disease induced by sulfur mustard(SM). Pulmonary disease was diagnosed as the most important disorder in individuals that had been exposed to sulfur mustard. Sulfur mustard is a chemical warfare agent...

PURPOSE Smad proteins mediate cellular signaling through the transforming growth factor-beta family (TGF-betas). Smads 2 and 3 transmit signals from TGF-beta, and Smad4 is a common mediator, as well. However, little is known concerning the expression patterns of Smads in lymphoid tissue. MATERIALS AND METHODS Immunohistochemistry for Smad3 and Smad4 was performed on paraffin-embedded tissue s...

Transforming growth factor-beta (TGF-beta) functions as a tumor suppressor of the prostate through mechanisms that remain unresolved. Although TGF-beta receptors directly activate both Smads 2 and 3, to date, Smad3 has been shown to be the essential mediator of most Smad-dependent TGF-beta responses, including control of gene expression, cell growth, apoptosis, and tumor suppression. Using a ro...

INTRODUCTION Bone Morphogenetic Proteins (BMPs) are members of the transforming growth factor-β superfamily and regulate cell growth, differentiation and development in many tissues. BMPs bind to type I and type II serine/threonine kinase receptors and transduce intracellular signals through Smad proteins. Smads can be classified into three subclasses, each with different roles in mediating sig...

Smad proteins form multimeric complexes consisting of the 'common partner' Smad4 and receptor regulated R-Smads on clustered DNA binding sites. Deciphering how pathway specific Smad complexes multimerize on DNA to regulate gene expression is critical for a better understanding of the cis-regulatory logic of TGF-β and BMP signaling. To this end, we solved the crystal structure of the dimeric Sma...

Objective: To investigate the expression of SMAD proteins in human thyroid tissues since the inactivation of TGF-b/activin signaling components is reported in several types of cancer. Phosphorylated SMAD 2 and SMAD3 (pSMAD2/3) associated with the SMAD4 induce the signal transduction generated by TGF-b and activin, while SMAD7 inhibits this intracellular signaling. Although TGF-b and activin exe...

TGF-β/Smads signaling plays a significant role in the regulation of growth of normal and prostate cancer cells. Smad proteins function as important mediators of intracellular signal transduction of transforming growth factor-β (TGF-β). TGF-β signaling pathway is known to regulate cell proliferation, differentiation, apoptosis and play a major role in some human diseases and cancers. Following t...

Kinase activation and substrate phosphorylation commonly form the backbone of signaling cascades. Bone morphogenetic proteins (BMPs), a subclass of TGF-β family ligands, induce activation of their signaling effectors, the Smads, through C-terminal phosphorylation by transmembrane receptor kinases. However, the slow kinetics of Smad activation in response to BMP suggests a preceding step in the ...