α1 Soluble Guanylyl Cyclase (sGC) Splice Forms as Potential Regulators of Human sGC Activity

摘要

Soluble guanylyl cyclase (sGC), a key protein in the NO/cGMP signaling pathway, is an obligatory heterodimeric protein composed of one α- and one β-subunit. The α1/β1 sGC heterodimer is the predominant form expressed in various tissues and is regarded as the major isoform mediating NO-dependent effects such as vasodilation. We have identified three new α1 sGC protein variants generated by alternative splicing. The 363 residue N1-α1 sGC splice variant contains the regulatory domain, the The sGC and an The sGC variant a of the regulatory and the of sGC sGC the of the α1 sGC splice in tissues of of the N1-α1 sGC protein a the of sGC the α1/β1 The sGC variant the and a and We by of the in the of α1 by of the and of splice the of sGC in Soluble guanylyl cyclase (sGC), a key protein in the NO/cGMP signaling pathway, is an obligatory heterodimeric protein composed of one α- and one β-subunit. The α1/β1 sGC heterodimer is the predominant form expressed in various tissues and is regarded as the major isoform mediating NO-dependent effects such as vasodilation. We have identified three new α1 sGC protein variants generated by alternative splicing. The 363 residue N1-α1 sGC splice variant contains the regulatory domain, the The sGC and an The sGC variant a of the regulatory and the of sGC sGC the of the α1 sGC splice in tissues of of the N1-α1 sGC protein a the of sGC the α1/β1 The sGC variant the and a and We by of the in the of α1 by of the and of splice the of sGC in the of the and the obligatory of the in mediating as an the of of the of in the and guanylyl cyclase guanylyl guanylyl The sGC heterodimer the The sGC in of by sGC of such as and protein the of sGC by of sGC The of sGC protein in a in of NO-dependent and of in the of of sGC of have identified and α1/β1 and by The α1/β1 sGC is the isoform and is in tissues the of in and and and The of α1/β1 sGC by the effects of major and in the α1 sGC of is by by of the of sGC and The of and and The of sGC is by and of and in by protein and the alternative the a variant and have a α1 sGC the in and sGC in splice variants of α1 sGC have the and of three new α1 sGC splice and We the splice form the sGC an in and splice variant is protein the N1-α1 sGC splice form the a α1/β1 sGC in The of sGC splice variant is and of tissues of the identified splice alternative of the α1 sGC a sGC and in and The a sGC the of the the of the and by N1-α1 sGC the and the the the and the the of in sGC the and the the of in the of sGC the and the the The of tissues of the a of and the the of an the and by the the of of in the α1 N1-α1 and sGC the The in in by the of of and of a and by a of in a an a and a and in a by of a and and of of the and by a a and in the the by of and The as the as the the in and a in in and have the the as of the in by the of an by a in The of in in of and and and in the by in and by The the of of and α1 sGC variants as and α1 the of the by in of the and The of and α1 sGC variants by and the of the of the and by the the the and by and The by α1 sGC identified by of the The α1 sGC identified sGC and the the sGC generated in sGC generated in and by and in of by and and The of protein and The protein three and by in of The three and the the The the and of sGC and in the α1 splice in the of sGC the The the α1 splice generated by the sGC the splice form the sGC and the splice form a of of of sGC guanylyl cyclase in of by of as The of as a and sGC as by and of and of α1 sGC in the the of alternative the α1 sGC in tissues We the α1 sGC a the splice variants of in identified α1 sGC tissues generated by alternative the α1 sGC of the α1 sGC of α1 alternative one of the identified α1 sGC the and the the of a protein 363 of α1 the of a and new and a We splice variant N1-α1 sGC sGC and and an and a in The protein the of the α1 an the and and identified α1 sGC splice of the regulatory and the the protein is by of one in the alternative splice in a in the The the alternative in splice variant in the al