The Conkright Laboratory
Research
Molecular Mechanisms of Cyclic AMP-Mediated Transcription
A gamut of biological functions are dependent on the cyclic AMP (cAMP) signaling cascade. These include but are not limited to: long-term memory, beta cell survival, glucose metabolism, cardiomyopathy, and chondrocyte proliferation. My laboratory studies the molecular mechanisms involved in the conversion of these cAMP signals into transcriptional events. Elevation in cellular cAMP stimulates the expression of numerous genes by liberating the catalytic subunits of Protein kinase A, which phosphorylates the transcription factor CREB (cAMP Responsive Element Binding-Protein). Phosphorylation of CREB promotes the recruitment of the co-activators CBP/P300 and the initiation of transcription. The diversity of biological functions associated with CREB and the cAMP pathway will be impossible to fully understand until all of the components involved in this pathway have been identified and characterized. Our laboratory is currently utilizing high-throughput cell based screening technologies available at the Scripps Florida campus (cDNA expression libraries, siRNA libraries, and small molecule libraries) to identify all of the proteins that comprise and regulate the cAMP pathway. We have already used this technology to identify TORCs, a novel family of CREB co-activators. Ascertaining the factors involved in the cAMP signaling pathway will be paramount in delineating why the biological function of CREB differs so drastically between tissues.
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