To evaluate the physiological functions of β1-, β2-, and β3-adrenoceptors (ARs) in brown adipose tissue, the lipolytic and respiratory effects of various adrenergic agonists and antagonists were studied in rat brown adipocytes. The β-agonists stimulated both lipolysis and respiration (8-10 times above basal levels), with the following order of potency (concentration eliciting 50% of maximum res...

The β-subunits of voltage-gated Ca (CaV) channels regulate the functional expression and several biophysical properties of highvoltage–activated CaV channels. We find that CaV β-subunits also determine channel regulation by the membrane phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2). When CaV1.3, -2.1, or -2.2 channels are cotransfected with the β3-subunit, a cytosolic protein, they ...

Diverse cellular TGF-β1 and TGF-β3 gene expression in normal human and murine lung. R.K. Coker, G.J. Laurent, S. Shahzeidi, N.A. Hernández-Rodríguez, P. Pantelidis, R.M. du Bois, P.K. Jeffery, R.J. McAnulty. ERS Journals Ltd 1996. ABSTRACT: A role for transforming growth factor-beta1 (TGF-β1) has been proposed in lung development and in the pathogenesis of pulmonary disease. However, previous ...

BACKGROUND Several phase II/III trials of anti-insulin-like growth factor 1 receptor (IGF-1R) monoclonal antibodies (mAbs) have shown limited efficacy. The mechanisms of resistance to IGF-1R mAb-based therapies and clinically applicable strategies for overcoming drug resistance are still undefined. METHODS IGF-1R mAb cixutumumab efficacy, alone or in combination with Src inhibitors, was evalu...

Mre11 plays an important role in repairing damaged DNA by cleaving broken ends and by providing a platform for other DNA repair proteins. Various Mre11 mutations have been identified in several types of cancer. We have determined the crystal structure of the human Mre11 core (hMre11), which contains the nuclease and capping domains. hMre11 dimerizes through the interfaces between loop β3-α3 fro...

Integrins are transmembrane receptors composed of α and β subunits. Although most integrins contain β1, canonical activation mechanisms are based on studies of the platelet integrin, αIIbβ3. Its inactive conformation is characterized by the association of the αIIb transmembrane and cytosolic domain (TM/CT) with a tilted β3 TM/CT that leads to activation when disrupted. We show significant struc...

Understanding how cells integrate multiple signaling pathways to achieve specific cell differentiation is a challenging question in cell biology. We have explored the physiological presentation of BMP-2 by using a biomaterial that harbors tunable mechanical properties to promote localized BMP-2 signaling. We show that matrix-bound BMP-2 is sufficient to induce β3 integrin-dependent C2C12 cell s...

Increasing energy expenditure through activation of endogenous brown adipose tissue (BAT) is a potential approach to treat obesity and diabetes. The class of β3-adrenergic receptor (AR) agonists stimulates rodent BAT, but this activity has never been demonstrated in humans. Here we determined the ability of 200 mg oral mirabegron (Myrbetriq, Astellas Pharma, Inc.), a β3-AR agonist currently app...

Hantaviruses are RNA viruses with known epidemic threat and potential for emergence. Several rodent-borne hantaviruses cause zoonoses accompanied by severe illness death. However, assessments of zoonotic risk the development countermeasures challenged our limited knowledge molecular mechanisms hantavirus infection, including identities cell entry receptors their roles in influencing viral host ...