Title

Signaling complexes of the FERM domain-containing protein GRSP1 bound to ARF exchange factor GRP1

UMMS Affiliation

Program in Molecular Medicine; Department of Biochemistry and Molecular Pharmacology

Publication Date

7-11-2001

Document Type

Article

Subjects

ADP-Ribosylation Factors; *Adaptor Proteins, Signal Transducing; Alternative Splicing; Amino Acid Sequence; Animals; Brain Chemistry; CHO Cells; Carrier Proteins; Cell Compartmentation; Cell Surface Extensions; Cricetinae; Lung; Mice; Molecular Sequence Data; Phosphatidylinositols; Protein Structure, Tertiary; Protein Transport; Receptor, Insulin; Receptors, Cytoplasmic and Nuclear; Signal Transduction; Tissue Distribution

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

GRP1 is a member of a family of proteins that contain a coiled-coil region, a Sec7 homology domain with guanosine nucleotide exchange activity for the ARF GTP-binding proteins, and a pleckstrin homology domain at the C terminus. The pleckstrin homology domain of GRP1 binds phosphatidylinositol (3,4,5) trisphosphate and mediates the translocation of GRP1 to the plasma membrane upon agonist stimulation of PI 3-kinase activity. Using a (32)P-labeled GRP1 probe to screen a mouse brain cDNA expression library, we isolated a cDNA clone encoding a GRP1-binding partner (GRSP1) that exists as two different splice variants in brain and lung. The GRSP1 protein contains a FERM protein interaction domain as well as two coiled coil domains and may therefore function as a scaffolding protein. Mapping experiments revealed that the interaction of GRP1 and GRSP1 occurs through the coiled coil domains in the two proteins. Immunodepletion experiments indicate that virtually all of the endogenous GRSP1 protein exists as a complex with GRP1 in lung. When co-expressed in Chinese hamster ovary cells expressing the human insulin receptor, both proteins display a diffuse, cytoplasmic localization. Acute translocation and co-localization of GRSP1 and GRP1 to ruffles in the plasma membrane was evident after insulin stimulation. These results identify GRSP1 as a novel member of GRP1 signaling complexes that are acutely recruited to plasma membrane ruffles in response to insulin receptor signaling.

Rights and Permissions

Citation: J Biol Chem. 2001 Oct 26;276(43):40065-70. Epub 2001 Jul 9. Link to article on publisher's site

DOI of Published Version

10.1074/jbc.M105260200

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

The Journal of biological chemistry

PubMed ID

11445584