| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
(Received for publication, December 14, 1995, and in revised form, April 25, 1996)
From the Department of Pharmacology, University of Pennsylvania
School of Medicine, Philadelphia, Pennsylvania 19104, The somatostatin (SRIF) receptors (SSTRs) 1 and 2 bind SRIF and SRIF 28 with high affinity, although a number of
synthetic hexapeptide and octapeptide analogs of SRIF bind selectively
to SSTR2. Extracellular loop three and its adjoining
trans-membrane-spanning regions contain elements essential for the
binding of such analogs to murine SSTR2. In particular, a stretch of
amino acids from residues 294-297 (FDFV) in murine SSTR2 in
trans-membrane domain seven can determine affinity for the
SSTR2-selective analogs. Within this region, Phe294 has
previously been predicted to be essential for the binding of
octapeptides (Kaupmann, K., Bruns, C., Raulf, F., Weber, H., Mattes,
H., and Lubbert, H. (1995) EMBO J. 14, 727-735) based on
the observation that SSTR1 can bind the octapeptide SMS-201-995 with
reasonable affinity after a Ser-to-Phe conversion in the analogous
region of this receptor (SSTR1S305F). We find that
SSTR1S305F has low affinity for a number of SSTR2-selective
hexapeptides, suggesting that these analogs have different binding
requirements than SMS-201-995. A correlation is seen between the
ability of SSTR1S305F to bind hexapeptide analogs and the
presence of a phenylalanine, but not tyrosine, at position two in these
small cyclic molecules. Thus, a single hydroxyl group in hexapeptides
can play a critical role in determining receptor binding to these
receptor mutants. We also find that the second extracellular loop of
SSTR1 is important for the selectivity of certain SRIF agonists for
binding to SSTR1. Taken together, our data indicate that there are
multiple elements in the somatostatin receptors that can determine the
binding affinity and selectivity of peptide analogs.
Volume 271, Number 34,
Issue of August 23, 1996
pp. 20331-20339
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
,
and
Protein Chemistry Department, Genentech, San Francisco,
California 94080, and § Peptide Biology Laboratory, The Salk
Institute, La Jolla, California 92037
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  V. Kundra, F. Mannting, A. G. Jones, and A. I. Kassis Noninvasive Monitoring of Somatostatin Receptor Type 2 Chimeric Gene Transfer J. Nucl. Med., March 1, 2002; 43(3): 406 - 412. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Sheridan, J. D. Kittilson, and B. J. Slagter Structure-Function Relationships of the Signaling System for the Somatostatin Peptide Hormone Family Integr. Comp. Biol., April 1, 2000; 40(2): 269 - 286. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Gether Uncovering Molecular Mechanisms Involved in Activation of G Protein-Coupled Receptors Endocr. Rev., February 1, 2000; 21(1): 90 - 113. [Abstract] [Full Text]
|
|
|
|
 |
|
 X. Lin, J. A. Janovick, S. Brothers, P. M. Conn, and R. E. Peter Molecular Cloning and Expression of Two Type One Somatostatin Receptors in Goldfish Brain Endocrinology, November 1, 1999; 140(11): 5211 - 5219. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. J. Mandell, K. A. Selz, and M. F. Shlesinger Mode matches and their locations in the hydrophobic free energy sequences of peptide ligands and their receptor eigenfunctions PNAS, December 9, 1997; 94(25): 13576 - 13581. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Baumeister and W. Meyerhof The POU Domain Transcription Factor Tst-1 Activates Somatostatin Receptor 1 Gene Expression in Pancreatic beta -Cells J. Biol. Chem., September 8, 2000; 275(37): 28882 - 28887. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
