The appearance of the first animal species on earth coincides with the emergence of transforming growth factor β (TGFβ) pathways. The evolution of these animals into more complex organisms coincides with a progressively increased TGFβ repertoire through gene duplications and divergence, making secreted TGFβ molecules the largest family of morphogenetic proteins in humans. It is therefore not su...

Transforming growth factor β (TGFβ) is the prototype member of a large superfamily of cytokines that also includes the bone morphogenic proteins (BMPs), growth and differentiation factors (GDFs) and activins. There are three genes for TGFβ in humans and mice (TGFβ1, TGFβ2 and TGFβ3) that each encode ~25 kDa mature, processed proteins and share over 70% identity in their amino acid sequences. De...

The most common vision-disrupting complication of cataract surgery is posterior capsule opacification (PCO; secondary cataract). PCO is caused by residual lens cells undergoing one of two very different cell fates: either transdifferentiating into myofibroblasts or maturing into lens fiber cells. Although TGFβ has been strongly implicated in lens cell fibrosis, the factors responsible for the l...

It is well established that transforming growth factor-β (TGFβ) switches its function from being a tumor suppressor to a tumor promoter during the course of tumorigenesis, which involves both cell-intrinsic and environment-mediated mechanisms. We are interested in breast cancer cells, in which SMAD mutations are rare and interactions between SMAD and other transcription factors define pro-oncog...

Cleft palate is one of the most common human birth defects and is associated with multiple genetic and environmental risk factors. Although mutations in the genes encoding transforming growth factor beta (TGFβ) signaling molecules and interferon regulatory factor 6 (Irf6) have been identified as genetic risk factors for cleft palate, little is known about the relationship between TGFβ signaling...

BACKGROUND Effective treatments for fibrotic diseases such as idiopathic pulmonary fibrosis are largely lacking. Transforming growth factor beta (TGFβ) plays a central role in the pathophysiology of fibrosis. We hypothesized that bone morphogenetic proteins (BMP), another family within the TGFβ superfamily of growth factors, modulate fibrogenesis driven by TGFβ. We therefore studied the role of...

T cells directed to endogenous tumor antigens are powerful mediators of tumor regression. Recent immunotherapy advances have identified effective interventions to unleash tumor-specific T-cell activity in patients who naturally develop them. Eliciting T-cell responses to a patient's individual tumor remains a major challenge. Radiation therapy can induce immune responses to model antigens expre...

mua-3 is a Caenorhabditis elegans homolog of the mammalian fibrillin1, a monogenic cause of Marfan syndrome. We identified a new mutation of mua-3 that carries an in-frame deletion of 131 amino acids in the extracellular domain, which allows the mutants to survive in a temperature-dependent manner; at the permissive temperature, the mutants grow normally without obvious phenotypes, but at the n...

Through differential screening between oyster families selected for high and low summer survival, we have characterized a new transforming growth factor-β (TGF-β) superfamily member. This novel factor, named oyster-gonadal-TGFβ-like (og-TGFβ-like), is synthesized as a 307 amino acid precursor and displays 6 of the 7 characteristic cysteine residues of the C-terminal, mature peptide. Sequence co...

Cell migration occurs by activation of complex regulatory pathways that are spatially and temporally integrated in response to extracellular cues. Binding of adenomatous polyposis coli (APC) to the microtubule plus ends in polarized cells is regulated by glycogen synthase kinase 3β (GSK-3β). This event is crucial for establishment of cell polarity during directional migration. However, the role...