Receptor Guanylyl Cyclase C
GC-C, a member of the family of membrane bound guanylyl cyclases, serves as the receptor for the family of endogenous guanylin peptides and the bacterial heat-stable enterotoxins. Activation of GC-C by ligand binding results in increases in intracellular cGMP levels, resulting in a cascade of cellular events, including activation of cyclic nucleotide-dependent protein kinases. The cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel, is phosphorylated by protein kinase A and G, resulting in increases chloride secretion, concomitant fluid efflux from the cell, and transitory diarrhea associated with the stable toxin peptides. Therefore, it is believed that the role of the guanylin family of peptides is to regulate fluid secretion across the intestinal epithelium, which is the major site for GC-C expression.
We have been studying the regulation, expression and down-stream signaling events mediated by GC-C as well as looking into its expression in extra-intestinal tissues. During the course of these studies, we have performed mutational analysis of the protein kinase-like domain of GC-C, generated polyclonal and monoclonal antibodies to various domains of GC-C, investigated the mechanism of transcriptional regulation of the GC-C gene, and investigated the role of glycosylation of GC-C in terms of its regulation and ligand-binding properties. More recently, we have studied the mechanisms of allosteric regulation of GC-C via the linker region. Importantly, we have identified cross-talk between c-src and GC-C mediated via tyrosine phosphorylation of GC-C, and this cross-talk regulates colon cell proliferation.
Visit the GC-C mini-molecule page on the Alliance for Cellular Signaling (AfCS) website.
Control PV + HgCl2
Cross-Talk between GC-C and c-Src Tyrosine Kinase
(Mol. Cell Biol. 2009 Oct;29(19):5277-89) (J. Mol. Evol. 2009 Jun;68(6):587-602)
Müller T, Rasool I, Heinz-Erian P, Mildenberger E, Hülstrunk C, Müller A, Michaud L, Koot BG, Ballauff A, Vodopiutz J, Rosipal S, Petersen BS, Franke A, Fuchs I, Witt H, Zoller H, Janecke AR, Visweswariah SS.
Congenital secretory diarrhoea caused by activating germline mutations in GUCY2C.
Basu N, Saha S, Khan I, Ramachandra SG, Visweswariah SS.
Intestinal Cell Proliferation and Senescence Are Regulated by Receptor Guanylyl Cyclase C and p21.
Arshad N, Visweswariah SS.
Arshad N, Ballal S, Visweswariah SS.
Site-specific N-linked glycosylation of receptor guanylyl cyclase C regulates ligand binding, ligand-mediated activation and interaction with vesicular integral membrane protein 36 (VIP36)
Arshad N, Visweswariah SS.
The multiple and enigmatic roles of guanylyl cyclase C in intestinal homeostasis.
Fiskerstrand T, Arshad N, Haukanes, BI, Tronstad RR, Pham KD, Johansson S, Havik B, Tonder SL, Levy SE, BrackmanD, Boman H, Biswas KH, Apold J, Hovdenak N, Visweswariah SS, Knappskog PM.
Basu N, Arshad N, Visweswariah SS.
Receptor guanylyl cyclase (GC-C): regulation and signal transduction.
Saha S, Biswas, KH, Kondapalli C, Isloor N, Visweswariah SS.
The linker region in receptor guanylyl cyclases is a key regulatory module: mutational analysis of guanylyl cyclase C.
Basu N, Bhandari R, Natarajan VT, Visweswariah SS.
Cross talk between receptor guanylyl cyclase C and c-src tyrosine kinase regulates colon cancer cell cytostasis.
Biswas, K.H., Shenoy, A.R., Dutta, A. and Visweswariah, S.S.
The evolution of guanylyl cyclases as multidomain proteins: conserved features of kinase-cyclase domain fusions.
J. Mol. Evol. 2009 Jun;68(6):587-602.
Jaleel M, Shenoy AR, Visweswariah SS.
Ghanekar Y, Chandrashaker A, Tatu U, Visweswariah SS.
Ghanekar Y, Chandrashaker A, Visweswariah
Jaleel M, London RM, Eber SL, Forte LR,
Bhandari R, Srinivasan N, Mahaboobi M,
Ghanekar Y, Suguna K, Visweswariah SS.
Roy N, Guruprasad MR, Kondaiah P, Mann EA,
Giannella RA, Visweswariah SS.
Vijayachandra K, Guruprasad M, Bhandari R,
Manjunath UH, Somesh BP, Srinivasan N, Suguna K, Visweswariah SS.
Bakre MM, Ghanekar Y, Visweswariah SS.
Nandi A, Bhandari R, Visweswariah SS.