PROINSULIN AND SOMATOSTATIN FROM THE ISLET ORGAN OF THE SOUTHERN-HEMISPHERE LAMPREY GEOTRIA-AUSTRALIS

An extract of the islet organ of the southern-hemisphere lamprey Geotr ia australis contained a high concentration of somatostatin-like immun oreactivity (34 nmol/g) but only trace amounts of insulin-like immunor eactivity. The primary structure of Geotria somatostatin-33 (AVQEAGGAA M(10)PPPGQRDRKA(20) GCKNFFWKTF(30)SSC) shows almost no similarity to s omatostatins from the holarctic lampreys Petromyzon marinus and Lampet ra fluviatilis in the N-terminal region but the functionally important C-terminal region, including the substitution Thr(31) --> Ser, is the same. Insulin was not identified in the extract but proinsulin and an incompletely processed form with an intact A-chain/C-peptide junction were purified and partially characterized. The primary structure of t he insulin region of Geotria proinsulin was established as A-chain; GI VEKCCHNR(10)CSIYQ MESYC(20)N; B-chain: SALTGSGGNY(10)LCGSYLVDAL(20)YLA CGPRGFF(30)YTSTPV. This sequence contains 17 amino acid substitutions compared with the identical insulins from P. marinus and L. fluviatili s but the unusual extension to the N-terminus of the B-chain (SALTG) i s present. Compared with mammalian insulins, Geotria insulin contains several substitutions of strongly conserved residues such as Gln(A5) - -> Lys in the putative receptor-binding region, Glu(B26) --> Pro impor tant in dimerization, and Leu(A13) --> Ile, His(B10) --> Tyr, and His( B21) --> Tyr important in hexamerization. Geotria proinsulin contains an Arg-Arg processing site at the B-chain/C-peptide junction but we sp eculate either that the Lys-Arg processing site at the C-peptide/A-cha in junction is absent or that the Geotria pancreas is unable to synthe size a SPC2-type prohormone convertase. Our results are consistent wit h the view that G. australis and holarctic lampreys arose from a commo n stock but have been separated for a considerable period. (C) 1995 Ac ademic Press, Inc.