A Family of cAMP-Binding Proteins That Directly Activate Rap1

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Science  18 Dec 1998:
Vol. 282, Issue 5397, pp. 2275-2279
DOI: 10.1126/science.282.5397.2275

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cAMP (3′,5′ cyclic adenosine monophosphate) is a second messenger that in eukaryotic cells induces physiological responses ranging from growth, differentiation, and gene expression to secretion and neurotransmission. Most of these effects have been attributed to the binding of cAMP to cAMP-dependent protein kinase A (PKA). Here, a family of cAMP-binding proteins that are differentially distributed in the mammalian brain and body organs and that exhibit both cAMP-binding and guanine nucleotide exchange factor (GEF) domains is reported. These cAMP-regulated GEFs (cAMP-GEFs) bind cAMP and selectively activate the Ras superfamily guanine nucleotide binding protein Rap1A in a cAMP-dependent but PKA-independent manner. Our findings suggest the need to reformulate concepts of cAMP-mediated signaling to include direct coupling to Ras superfamily signaling.

  • * To whom correspondence should be addressed at the Department of Brain and Cognitive Sciences, Building E25, Room 618, MIT, Cambridge, MA 02139, USA. E-mail: amg{at}

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