T cell-intrinsic transforming growth factor β (TGFβ) receptor signaling plays an essential role in controlling immune responses. The RING-type E3 ligase Cbl-b has been shown to mediate the sensitivity of T cells to TGFβ; however, the mechanism underlying this process is unknown. This study shows that SMAD7, an established negative regulator of TGFβ receptor (TGFβR) signaling, is a key downstrea...

Bone morphogenetic proteins (BMPs) are members of the TGFβ growth factor superfamily and have important roles in proliferation, development, differentiation of embryonic and adult cells, as well as in tissue regeneration. BMPs signal via two transmembrane serine/threonine kinase receptors, the BMP type I (BMPRIa and BMPRIb) and BMP type II (BMPRII) receptors which can form homoand heterooligome...

Secreted cytokines of the TGFβ family are found in all multicellular organisms and implicated in regulating fundamental cell behaviors such as proliferation, differentiation, migration and survival. Signal transduction involves complexes of specific type I and II receptor kinases that induce the nuclear translocation of Smad transcription factors to regulate target genes. Ligands of the BMP and...

OBJECTIVE To delineate the constitutive pulmonary vascular phenotype of the TβRIIΔk-fib mouse model of scleroderma, and to selectively induce pulmonary endothelial cell injury using vascular endothelial growth factor (VEGF) inhibition to develop a model with features characteristic of pulmonary arterial hypertension (PAH). METHODS The TβRIIΔk-fib mouse strain expresses a kinase-deficient tran...

(TGFβ) is a major contributing factor to many diseases including progressive cancers [1]. Given the normal homeostatic functions of TGFβ in controlling cell proliferation, immune surveillance and angiogenesis, however, it is much less clear which cancer patients would derive clinical benefit from the administration of anti-TGFβ targeted therapy. The use of these therapies is complicated not onl...

1 BAMBI acts as a pseudoreceptor for the TGFβ type I receptor family and negative modulator of TGFβ kinase 2 signaling and BAMBI-/-mice show mild endothelial dysfunction. As diabetic glomerular disease is associated 3 with TGFβ overexpression and microvascular alterations, we examined the effect of diabetes on glomerular 4 BAMBI mRNA levels. In isolated glomeruli from biopsies of patients with ...

The transforming growth factor-β (TGFβ) family signaling pathways play an important role in regulatory cellular networks and exert specific effects on developmental programs during embryo development. However, the function of TGFβ signaling pathways on the early kidney development remains unclear. In this work, we aim to detect the underlying role of TGFβ type II receptor (TβRII) in vitro, whic...

Apoptosis or programmed cell death is a major mechanism underlying morphogenetic events that sculpt the developing embryo. Prominent examples of cell death during vertebrate development include refinement of the immune system, specification of neuronal projections, formation of digits, and tail resorption during amphibian metamorphosis (see Jacobson et al., 1997). Müllerian duct regression is a...