Truncated IRAG variants modulate cGMP mediated inhibition of human colonic smooth muscle cell contraction

Nitric oxide (NO) mediates relaxation of colonic smooth muscle cells predominantly by cGMP/cGMP-dependent protein kinase I (cGKI)-induced phosphorylation of the IP3R-associated cGMP kinase substrate (IRAG) to block store-dependent calcium signaling. In the present study we analyzed the structure and function of the human IRAG gene. We describe four unique first exon variants transcribed from individual promoters in diverse human tissues. Tissue specific alternative splicing with exon skipping and alternative splice donor and acceptor site usage further increases diversity of IRAG mRNA variants that encode for N-…