Transforming growth factor-β (TGF-β) superfamily is a key player in the regulation of a wide variety of physiological processes from development to pathogenesis. Since the discovery of the prototypic member, TGF-β, almost three decades ago, there have been tremendous advances in our understanding of its complex biology. TGF-β misregulation has been implicated in the pathogenesis of a variety of...

transforming growth factor betas are multifunctional polypeptides in the cytokine superfamily. they have a growth inhibitory role on hemopoietic progenitor cells in semisolid colony assay as well as in long-term bone-marrow culture. tgf - β2 represses stromal cells, stem cell factor gene transcription, and decreases the stability of c-kit transcripts in hemopoietic cells. tgf-β also modulates g...

Transforming Growth Factor-β (TGF-β) signaling in cancer has been termed the "TGF-β paradox", acting as both a tumor suppresser and promoter. The complexity of TGF-β signaling within the tumor is context dependent, and greatly impacted by cellular crosstalk between TGF-β responsive cells in the microenvironment including adjacent epithelial, endothelial, mesenchymal, and hematopoietic cells. He...

background and objective : narcolepsy is a chronic neurological disorder caused by loss of hypocretin (hcrt) neurons. both genetic and environmental factors play an important role for the development of narcolepsy. the mechanism of hcrt loss in narcolepsy is elusive; however, an autoimmune mediated destruction of hcrt neurons is suspected. the purpose of this study was to assess th17 related cy...

Proliferation of pancreatic β-cells is an important mechanism underlying β-cell mass adaptation to metabolic demands. Increasing β-cell mass by regeneration may ameliorate or correct both type 1 and type 2 diabetes, which both result from inadequate production of insulin by β-cells of the pancreatic islet. Transforming growth factor β (TGF-β) signaling is essential for fetal development and gro...

Transforming growth factor-β (TGF-β) is generally considered as a central mediator of fibrotic diseases. Indeed, much focus has been placed on inhibiting TGF-β and its downstream targets as ideal therapeutic strategies. However, pharmacological blockade of TGF-β has not yet translated into successful therapy for humans, which may be due to pleiotropic effects of TGF-β signaling. Equally, TGF-β ...

DGK-ζ is a negative regulator of TCR signaling that causes degradation of the second messenger DAG, terminating DAG-mediated activation of Ras and PKCθ. Cytotoxic T cells deficient in DGK-ζ demonstrate enhanced effector functions in vitro and antitumor activity in vivo, perhaps because of insensitivity to inhibitory cytokines. We sought to determine whether the enhanced responsiveness of DGK-ζ-...

Transforming growth factor β (TGF-β) isoforms are secreted as inactive complexes formed through noncovalent interactions between the bioactive TGF-β entity and its N-terminal latency-associated peptide prodomain. Extracellular activation of the latent TGF-β complex is a crucial step in the regulation of TGF-β function for tissue homeostasis. We show that the fibrinogen-like (FBG) domain of the ...

The amplitude of transforming growth factor-β (TGF-β) signal is tightly regulated to ensure appropriate physiological responses. As part of negative feedback loop SMAD7, a direct transcriptional target of downstream TGF-β signaling acts as a scaffold to recruit the E3 ligase SMURF2 to target the TGF-β receptor complex for ubiquitin-mediated degradation. Here, we identify the deubiquitinating en...