Abstract: Regulatory elements responsible for tissue-specific transcriptional regulation of the human ?3-adrenergic receptor (?3-AR) were identified. A region localized between ?6.50 and ?6.30 kb of the proximal promoter contained three sequences that act synergistically to achieve full transcriptional activity. One segment, termed segment A, contains an Sp1 binding site. Another of the sequences, termed segment B, is a binding site for a trans-acting factor present in cells that constitutively express ?3-AR. In a specific embodiment, the trans-acting factor is expressed in neuroblastoma (SK-N-MC) and brown adipose tissue cells, but little or not at all in CV-1, HeLa, or white adipose tissue cells. The third segment, C, is an S1 nuclease-sensitive site having CCTT repeats.

Abstract: A screening assay in yeast is disclosed wherein G-protein coupled-receptor independent activators and inhibitors of the pheromone pathway can be identified using a mammalian cDNA library. Novel Activator of G protein Signaling (“AGS”) proteins, which are Ras-related proteins that stimulate G protein activity in a receptor-independent manner, are disclosed, as well as nucleic acid molecules encoding AGS proteins. In addition to isolated AGS proteins, the invention further provides isolated AGS fusion proteins, antigenic peptides and anti-AGS antibodies. The invention also provides isolated AGS nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced and non-human transgenic animals in which an AGS gene has been introduced or disrupted. Diagnostic, screening and therapeutic methods utilizing compositions of the invention are also provided.

Abstract: Regulatory elements responsible for tissue-specific transcriptional regulation of the human &bgr;3-adrenergic receptor (&bgr;3-AR) were identified. A region localized between −6.50 and −6.30 kb of the proximal promoter contained three sequences that act synergistically to achieve full transcriptional activity. One segment, termed segment A, contains an Sp1 binding site. Another of the sequences, termed segment B, is a binding site for a trans-acting factor present in cells that constitutively express &bgr;3-AR. In a specific embodiment, the trans-acting factor is expressed in neuroblastoma (SK-N-MC) and brown adipose tissue cells, but little or not at all in CV-1, HeLa, or white adipose tissue cells. The third segment, C, is an S1 nuclease-sensitive site having CCTT repeats.

Abstract: A screening assay in yeast is disclosed wherein G-protein coupled-receptor independent activators and inhibitors of the pheromone pathway can be identified using a mammalian cDNA library. Novel Activator of G protein Signaling (“AGS”) proteins, which are Ras-related proteins that stimulate G protein activity in a receptor-independent manner, are disclosed, as well as nucleic acid molecules encoding AGS proteins. In addition to isolated AGS proteins, the invention further provides isolated AGS fusion proteins, antigenic peptides and anti-AGS antibodies. The invention also provides isolated AGS nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced and non-human transgenic animals in which an AGS gene has been introduced or disrupted. Diagnostic, screening and therapeutic methods utilizing compositions of the invention are also provided.

Abstract: Regulatory elements responsible for tissue-specific transcriptional regulation of the human &bgr;3-adrenergic receptor (&bgr;3-AR) were identified. A region localized between −6.50 and −6.30 kb of the proximal promoter contained three sequences that act synergistically to achieve full transcriptional activity. One segment, termed segment A, contains an Sp1 binding site. Another of the sequences, termed segment B, is a binding site for a trans-acting factor present in cells that constitutively express &bgr;3-AR. In a specific embodiment, the trans-acting factor is expressed in neuroblastoma (SK-N-MC) and brown adipose tissue cells, but little or not at all in CV-1, HeLa, or white adipose tissue cells. The third segment, C, is an S1 nuclease-sensitive site having CCTT repeats.

Abstract: The invention provides isolated AGS nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, including AGS specific promoters, host cells into which the expression vectors have been introduced, and a process of transcribing or expressing a heterologous sequence by culturing the host cells under appropriate conditions.

Abstract: A screening assay in yeast is disclosed wherein G-protein coupled-receptor independent activators and inhibitors of the pheromone pathway can be identified using a mammalian cDNA library. Novel Activator of G protein Signaling (“AGS”) proteins, which are Ras-related proteins that stimulate G protein activity in a receptor-independent manner, are disclosed, as well as nucleic acid molecules encoding AGS proteins. In addition to isolated AGS proteins, the invention further provides isolated AGS fusion proteins, antigenic peptides and anti-AGS antibodies. The invention also provides isolated AGS nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced and non-human transgenic animals in which an AGS gene has been introduced or disrupted. Diagnostic, screening and therapeutic methods utilizing compositions of the invention are also provided.

Abstract: Regulatory elements responsible for tissue-specific transcriptional regulation of the human &bgr;3-adrenergic receptor (&bgr;3-AR) were identified. A region localized between −6.50 and −6.30 kb of the proximal promoter contained three sequences that act synergistically to achieve full transcriptional activity. One segment, termed segment A, contains an Sp1 binding site. Another of the sequences, termed segment B, is a binding site for a trans-acting factor present in cells that constitutively express &bgr;3-AR. In a specific embodiment, the trans-acting factor is expressed in neuroblastoma (SK-N-MC) and brown adipose tissue cells, but little or not at all in CV-1, HeLa, or white adipose tissue cells. The third segment, C, is an S1 nuclease-sensitive site having CCTT repeats.

Abstract: Regulatory elements responsible for tissue-specific transcriptional regulation of the human &bgr;3-adrenergic receptor (&bgr;3-AR) were identified. A region localized between −6.50 and −6.30 kb of the proximal promoter contained three sequences that act synergistically to achieve full transcriptional activity. One segment, termed segment A, contains an Sp 1 binding site. Another of the sequences, termed segment B, is a binding site for a trans-acting factor present in cells that constitutively express &bgr;3-AR. In a specific embodiment, the trans-acting factor is expressed in neuroblastoma (SK-N-MC) and brown adipose tissue cells, but little or not at all in CV-1, HeLa, or white adipose tissue cells. The third segment, C, is an S1 nuclease-sensitive site having CCTT repeats.