PMID: 7539143May 23, 1995Paper

Regulation of cell signaling by the cytoplasmic domains of the heat-stable enterotoxin receptor: identification of autoinhibitory and activating motifs

Proceedings of the National Academy of Sciences of the United States of America
X L RudnerJ S Almenoff

Abstract

Infection with enterotoxigenic Escherichia coli is a leading cause of traveler's diarrhea. Many enterotoxigenic E. coli strains produce heat-stable enterotoxin (ST), a peptide that binds to the intestinal receptor guanylyl cyclase C known as STaR. The toxin-receptor interaction elevates intracellular cGMP, which then activates apical chloride secretion, resulting in secretory diarrhea. In this report, we examine how the intracellular domains of STaR participate in the propagation and regulation of signaling. We show that STaR exists as an oligomer in both the presence and the absence of toxin. We also demonstrate that deletion of the intracellular kinase-homology domain produces a constitutively active mutant, suggesting that this domain subserves an autoinhibitory function. Finally, we constructed a point mutant within a highly conserved region of the cyclase domain that completely inactivates the catalytic activity of guanylyl cyclase. Cotransfection of this point mutant with wild-type receptor causes a dominant-negative effect on receptor activation. This suggests that interaction of receptor subunits is required for toxin-induced activation and that the cyclase domain is involved in this essential interaction. We propose th...Continue Reading

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Citations

Jul 1, 1996·Protein Science : a Publication of the Protein Society·P BorkJ Schultz
Oct 9, 2008·Proceedings of the National Academy of Sciences of the United States of America·Annika RauchClemens Steegborn
Jun 3, 2005·Zoological Science·Mina Nakauchi, Norio Suzuki
Oct 8, 2009·Comparative and Functional Genomics·K AnamikaN Srinivasan
Apr 16, 1998·Microbial Pathogenesis·G B Nair, Y Takeda
Dec 6, 2003·Acta Physiologica Scandinavica·A-M LahtiP Tarnow
Dec 5, 2009·Molecular and Cellular Biochemistry·Nirmalya BasuSandhya S Visweswariah
Jun 27, 1998·Toxicon : Official Journal of the International Society on Toxinology·M R Popoff
Mar 1, 1996·Microbiological Reviews·C L Sears, J B Kaper

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