Abstract: Stress responses involve corticotropin releasing factor (CRF), the two cognate receptors (CRF1 and CRF2) and the CRF-binding protein (CRFBP). Utilizing a novel cell-based assay, a C-terminal CRFBP fragment [CRFBP(10 kD)] was found to potentiates CRF-intracellular Ca2+ release, demonstrating that CRFBP possesses excitatory roles in addition to the inhibitory role established by the N-terminal fragment of CRFBP [CRFBP(27 kD)]. This interaction was CRF2-specific, as CRF1 responses were not potentiated by CRFBP(10 kD). As there were currently no small molecule ligands available that selectively interact with either CRFBP or CRF2, a cell-based assay was miniaturized, wherein CRFBP(10 kD) was fused as a chimera with CRF2?, that allowed us to a perform a high-throughput screen (HTS) of approximately 350,000 small molecules.

Abstract: Stress responses involve corticotropin releasing factor (CRF), the two cognate receptors (CRF1 and CRF2) and the CRF-binding protein (CRFBP). Utilizing a novel cell-based assay, a C-terminal CRFBP fragment [CRFBP (10 kD)] was found to potentiates CRF-intracellular Ca2+ release, demonstrating that CRFBP possesses excitatory roles in addition to the inhibitory role established by the N-terminal fragment of CRFBP [CRFBP (27 kD)]. This interaction was CRF2-specific, as CRF1 responses were not potentiated by CRFBP (10 kD). As there were currently no small molecule ligands available that selectively interact with either CRFBP or CRF2?, a cell-based assay was miniaturized, wherein CRFBP (10 kD) was fused as a chimera with CRF2?, that allowed us to a perform a high-throughput screen (HTS) of approximately 350,000 small molecules.

Abstract: Stress responses involve corticotropin releasing factor (CRF), the two cognate receptors (CRF1 and CRF2) and the CRF-binding protein (CRFBP). Utilizing a novel cell-based assay, a C-terminal CRFBP fragment [CRFBP(10 kD)] was found to potentiates CRF-intracellular Ca2+ release, demonstrating that CRFBP possesses excitatory roles in addition to the inhibitory role established by the N-terminal fragment of CRFBP [CRFBP(27 kD)]. This interaction was CRF2-specific, as CRF1 responses were not potentiated by CRFBP(10 kD). As there were currently no small molecule ligands available that selectively interact with either CRFBP or CRF2, a cell-based assay was miniaturized, wherein CRFBP(10 kD) was fused as a chimera with CRF2?, that allowed us to a perform a high-throughput screen (HTS) of approximately 350,000 small molecules.

Abstract: Stress responses involve corticotropin releasing factor (CRF), the two cognate receptors (CRF1 and CRF2) and the CRF-binding protein (CRFBP). Utilizing a novel cell-based assay, a C-terminal CRFBP fragment [CRFBP(10 kD)] was found to potentiates CRF-intracellular Ca2+ release, demonstrating that CRFBP possesses excitatory roles in addition to the inhibitory role established by the N-terminal fragment of CRFBP [CRFBP(27 kD)]. This interaction was CRF2-specific, as CRF1 responses were not potentiated by CRFBP(10 kD). As there were currently no small molecule ligands available that selectively interact with either CRFBP or CRF2, a cell-based assay was miniaturized, wherein CRFBP(10 kD) was fused as a chimera with CRF2?, that allowed us to a perform a high-throughput screen (HTS) of approximately 350,000 small molecules.