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 Geotria australis contained a high concentration of somatostatin-like immunoreactivity (34 nmol/g) but only trace amounts of insulin-like immunoreactivity. The primary structure of Geotria somatostatin-33 (AVQEAGGAAM10PPPGQRDRKA20GCKNFFWKTF30SSC) shows almost no similarity to somatostatins from the holarctic lampreys Petromyzon marinus and Lampetra fluviatilis in the N-terminal region but the functionally important C-terminal region, including the substitution Thr31 --> 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 the insulin region of Geotria proinsulin was established as A-chain; GIVEKCCHNR10CSIYQ MESYC20N; B-chain: SALTGSGGNY10LCGSYLVDAL20YLACGPRGFF30YTSTPV. This sequence contains 17 amino acid substitutions compared with the identical insulins from P. marinus and L. fluviatilis but the unusual extension to the N-terminus of the B-chain (SALTG) is 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 important 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 speculate either that the Lys-Arg processing site at the C-peptide/A-chain junction is absent or that the Geotria pancreas is unable to synthesize a SPC2-type prohormone convertase. Our results are consistent with the view that G. australis and holarctic lampreys arose from a common stock but have been separated for a considerable period.
Conlon
J M
JM
Department of Biomedical Sciences, Creighton University, Omaha, Nebraska 68178, USA.
Nielsen
P F
PF
Youson
J H
JH
Potter
I C
IC
D000595:Amino Acid Sequence; D000818:Animals; D007515:Islets of Langerhans / Q000737:chemistry*; D007798:Lampreys; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D011384:Proinsulin / Q000235:genetics / Q000302:isolation & purification*; D011863:Radioimmunoassay; D013004:Somatostatin / Q000235:genetics / Q000302:isolation & purification*
D013004:Somatostatin; D011384:Proinsulin