Somatostatin Receptor Interacting Protein Defines a Novel Family of Multidomain Proteins Present in Human and Rodent Brain*
- From the Institut für Zellbiochemie und Klinische Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Universität Hamburg, Martinistrasse 52, 20246 Hamburg, Germany
Abstract
By using the yeast two-hybrid system we identified a novel protein from the human brain interacting with the C terminus of somatostatin receptor subtype 2. This protein termed somatostatin receptor interacting protein is characterized by a novel domain structure, consisting of six N-terminal ankyrin repeats followed by SH3 and PDZ domains, several proline-rich regions, and a C-terminal sterile α motif. It consists of 2185 amino acid residues encoded by a 9-kilobase pair mRNA; several splice variants have been detected in human and rat cDNA libraries. Sequence comparison suggests that the novel multidomain protein, together with cortactin-binding protein, forms a family of cytoskeletal anchoring proteins. Fractionation of rat brain membranes indicated that somatostatin receptor interacting protein is enriched in the postsynaptic density fraction. The interaction of somatostatin receptor subtype 2 with its interacting protein was verified by overlay assays and coimmunoprecipitation experiments from transfected human embryonic kidney cells. Somatostatin receptor subtype 2 and the interacting protein display a striking overlap of their expression patterns in the rat brain. Interestingly, in the hippocampus the mRNA for somatostatin receptor interacting protein was not confined to the cell bodies but was also observed in the molecular layer, suggesting a dendritic localization of this mRNA.
Footnotes
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↵* This work was supported by Deutsche Forschungsgemeinschaft Grant SFB545/B7 (to H.-J. K. and D. R.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‡ Presented this work as part of a thesis.
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↵§ To whom correspondence should be addressed: Institut für Zellbiochemie und Klinische Neurobiologie, UKE, Martinistrasse 52, 20246 Hamburg, Germany. Tel.: 49 40 42803 3344; Fax: 49 40 42803 4541;E-mail: richter@uke.uni-hamburg.de.
- Abbreviations:
- PDZ
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PSD-95/discs large/ZO-1
- CortBP1
-
cortactin-binding protein 1
- GST
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glutathioneS-transferase
- HEK
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human embryonic kidney
- PSD
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postsynaptic density
- SAM
-
sterile α motif
- SAP102
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synapse-associated protein 102
- SH3
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Src homology 3
- SSTR
-
somatostatin receptor
- SSTRIP
-
somatostatin receptor interacting protein
- kb
-
kilobase pairs
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- Received June 29, 1999.
- Revision received September 7, 1999.
- The American Society for Biochemistry and Molecular Biology, Inc.
