Brian K. Kobilka

Overexpression of angiotensin AT1 receptor transgene in the mouse myocardium produces a lethal phenotype associated with myocyte hyperplasia and heart block

Hein, Lutz, Stevens, Mary E., Barsh, Gregory S., Pratt, Richard E., Kobilka, Brian K., Dzau, Victor J.

Previous studies have suggested that angiotensin II (Ang II) modulates cardiac contractility, rhythm, metabolism, and structure. However, it is unclear whether the cardiac effects are due to direct...

Dual modulation of cell survival and cell death by β2-adrenergic signaling in adult mouse cardiac myocytes

Zhu, Wei-Zhong, Zheng, Ming, Koch, Walter J., Lefkowitz, Robert J., Kobilka, Brian K., Xiao, Rui-Ping

The goal of this study was to determine whether β1-adrenergic receptor (AR) and β2-AR differ in regulating cardiomyocyte survival and apoptosis and, if so, to explore underlying mechanisms. One...

Agonist-induced conformational changes in the G-protein-coupling domain of the β2 adrenergic receptor

Ghanouni, Pejman, Steenhuis, Jacqueline J., Farrens, David L., Kobilka, Brian K.

The majority of extracellular physiologic signaling molecules act by stimulating GTP-binding protein (G-protein)-coupled receptors (GPCRs). To monitor directly the formation of the active state of a...

Single-molecule spectroscopy of the β2 adrenergic receptor: Observation of conformational substates in a membrane protein

Peleg, Gadi, Ghanouni, Pejman, Kobilka, Brian K., Zare, Richard N.

Single-molecule studies of the conformations of the intact β2 adrenergic receptor were performed in solution. Photon bursts from the fluorescently tagged adrenergic receptor in a micelle were...

Heterozygous α2A-adrenergic receptor mice unveil unique therapeutic benefits of partial agonists

Tan, Christopher M., Wilson, Matthew H., MacMillan, Leigh B., Kobilka, Brian K., Limbird, Lee E.

Genetic manipulation of the α2A-adrenergic receptor (α2A-AR) in mice has revealed the role of this subtype in numerous responses, including agonist-induced hypotension and sedation. Unexpectedly,...

Linkage of β1-adrenergic stimulation to apoptotic heart cell death through protein kinase A–independent activation of Ca2+/calmodulin kinase II

Zhu, Wei-Zhong, Wang, Shi-Qiang, Chakir, Khalid, Yang, Dongmei, Zhang, Tong, Brown, Joan Heller, ...

β1-adrenergic receptor (β1AR) stimulation activates the classic cAMP/protein kinase A (PKA) pathway to regulate vital cellular processes from the change of gene expression to the control of...

Antithetic regulation by β-adrenergic receptors of Gq receptor signaling via phospholipase C underlies the airway β-agonist paradox

McGraw, Dennis W., Almoosa, Khalid F., Paul, Richard J., Kobilka, Brian K., Liggett, Stephen B.

β-adrenergic receptors (βARs) relax airway smooth muscle and bronchodilate, but chronic β-agonist treatment in asthma causes increased sensitivity to airway constriction (hyperreactivity) and is...

A fluorescent probe designed for studying protein conformational change

Cohen, Bruce E., Pralle, Arnd, Yao, XiaoJie, Swaminath, Gayathri, Gandhi, Chris S., Jan, Yuh Nung, ...

The usefulness of fluorescence in studying protein motions derives from its sensitivity, kinetic resolution, and compatibility with both live cells and physiological assays. Recent advances in...

Overexpression of angiotensin AT1 receptor transgene in the mouse myocardium produces a lethal phenotype associated with myocyte hyperplasia and heart block

Hein, Lutz, Stevens, Mary E., Barsh, Gregory S., Pratt, Richard E., Kobilka, Brian K., Dzau, Victor J.

Previous studies have suggested that angiotensin II (Ang II) modulates cardiac contractility, rhythm, metabolism, and structure. However, it is unclear whether the cardiac effects are due to direct...

Dual modulation of cell survival and cell death by β2-adrenergic signaling in adult mouse cardiac myocytes

Zhu, Wei-Zhong, Zheng, Ming, Koch, Walter J., Lefkowitz, Robert J., Kobilka, Brian K., Xiao, Rui-Ping

The goal of this study was to determine whether β1-adrenergic receptor (AR) and β2-AR differ in regulating cardiomyocyte survival and apoptosis and, if so, to explore underlying mechanisms. One...

Agonist-induced conformational changes in the G-protein-coupling domain of the β2 adrenergic receptor

Ghanouni, Pejman, Steenhuis, Jacqueline J., Farrens, David L., Kobilka, Brian K.

The majority of extracellular physiologic signaling molecules act by stimulating GTP-binding protein (G-protein)-coupled receptors (GPCRs). To monitor directly the formation of the active state of a...

Single-molecule spectroscopy of the β2 adrenergic receptor: Observation of conformational substates in a membrane protein

Peleg, Gadi, Ghanouni, Pejman, Kobilka, Brian K., Zare, Richard N.

Single-molecule studies of the conformations of the intact β2 adrenergic receptor were performed in solution. Photon bursts from the fluorescently tagged adrenergic receptor in a micelle were...

Heterozygous α2A-adrenergic receptor mice unveil unique therapeutic benefits of partial agonists

Tan, Christopher M., Wilson, Matthew H., MacMillan, Leigh B., Kobilka, Brian K., Limbird, Lee E.

Genetic manipulation of the α2A-adrenergic receptor (α2A-AR) in mice has revealed the role of this subtype in numerous responses, including agonist-induced hypotension and sedation. Unexpectedly,...

Linkage of β1-adrenergic stimulation to apoptotic heart cell death through protein kinase A–independent activation of Ca2+/calmodulin kinase II

Zhu, Wei-Zhong, Wang, Shi-Qiang, Chakir, Khalid, Yang, Dongmei, Zhang, Tong, Brown, Joan Heller, ...

β1-adrenergic receptor (β1AR) stimulation activates the classic cAMP/protein kinase A (PKA) pathway to regulate vital cellular processes from the change of gene expression to the control of...

Antithetic regulation by β-adrenergic receptors of Gq receptor signaling via phospholipase C underlies the airway β-agonist paradox

McGraw, Dennis W., Almoosa, Khalid F., Paul, Richard J., Kobilka, Brian K., Liggett, Stephen B.

β-adrenergic receptors (βARs) relax airway smooth muscle and bronchodilate, but chronic β-agonist treatment in asthma causes increased sensitivity to airway constriction (hyperreactivity) and is...

A fluorescent probe designed for studying protein conformational change

Cohen, Bruce E., Pralle, Arnd, Yao, XiaoJie, Swaminath, Gayathri, Gandhi, Chris S., Jan, Yuh Nung, ...

The usefulness of fluorescence in studying protein motions derives from its sensitivity, kinetic resolution, and compatibility with both live cells and physiological assays. Recent advances in...

Organization of β-adrenoceptor signaling compartments by sympathetic innervation of cardiac myocytes

Shcherbakova, Olga G., Hurt, Carl M., Xiang, Yang, Dell'Acqua, Mark L., Zhang, Qi, Tsien, Richard W., ...

The sympathetic nervous system regulates cardiac function through the activation of adrenergic receptors (ARs). β1 and β2ARs are the primary sympathetic receptors in the heart and play different...

Dosage-dependent switch from G protein-coupled to G protein-independent signaling by a GPCR

Sun, Yutong, Huang, Jianyun, Xiang, Yang, Bastepe, Murat, Jüppner, Harald, Kobilka, Brian K, ...

G-protein-coupled receptors (GPCRs) mostly signal through heterotrimeric G proteins. Increasing evidence suggests that GPCRs could function in a G-protein-independent manner. Here, we show that at...

Structure-based discovery of β2-adrenergic receptor ligands

Kolb, Peter, Rosenbaum, Daniel M., Irwin, John J., Fung, Juan José, Kobilka, Brian K., Shoichet, Brian K.

Aminergic G protein-coupled receptors (GPCRs) have been a major focus of pharmaceutical research for many years. Due partly to the lack of reliable receptor structures, drug discovery efforts have...

Ligand-regulated oligomerization of β2-adrenoceptors in a model lipid bilayer

Fung, Juan José, Deupi, Xavier, Pardo, Leonardo, Yao, Xiao Jie, Velez-Ruiz, Gisselle A, DeVree, Brian T, ...

The β2-adrenoceptor (β2AR) was one of the first Family A G protein-coupled receptors (GPCRs) shown to form oligomers in cellular membranes, yet we still know little about the number and arrangement...