Abstract
Regulation of heterotrimeric G protein βγ subunits mediated PI3K activation and leukocyte migration through a novel WD40‐WD40 repeat interaction between RACK1 and Gβγ
The FASEB journal, Vol.21(5), pp.A616-A617
04/2007
DOI: 10.1096/fasebj.21.5.A616-c
Abstract
Many chemoattractants act through G protein-mediated pathways to regulate leukocyte migration. Heterotrimeric G protein βγ subunits released from the activated Gi/o family of G proteins act as a molecular switch to trigger the activation of key signaling molecules such as PI3K to promote chemoattractant-mediated directional cell migration. Here we describe the discovery of a novel mechanism of regulating leukocyte migration through the interaction of Gβγ with RACK1, receptor for activated C kinase 1, which is a novel binding partner of Gβγ that we previously identified and is a member of WD40 repeat proteins as is Gβ. We showed that RACK1 binds Gβγ through a novel WD40-WD40 repeat interaction and its N-terminal domain is the major determinant for binding Gβγ. Binding of full-length RACK1 or its N-terminal fragment to Gβγ inhibits Gβγ-stimulated PI3Kγ activity in vitro due to the partial overlap of RACK1 and PI3Kγ binding sites on Gβγ as determined by using peptides derived from Gβ. Silencing RACK1 specifically enhances chemoattractant-induced PI3K activation and concomitantly, chemotaxis of Jurkat and differentiated HL60 cells. Conversely, overexpression of RACK1 or its N-terminal fragment reduces PI3K activity and cell motility. These findings indicate that RACK1 represents a novel regulatory protein involved in negatively modulating Gβγ-mediated chemotaxis of leukocytes through PI3K.
Details
- Title: Subtitle
- Regulation of heterotrimeric G protein βγ subunits mediated PI3K activation and leukocyte migration through a novel WD40‐WD40 repeat interaction between RACK1 and Gβγ
- Creators
- Songhai Chen - Departmento of PharmacologyVanderbilt UniversityRoom 444, RRB, 21st Ave@Pierce Dr.NashvilleTN37232Fang Lin - Vanderbilt University21st Ave@Pierce Dr., Nashville, TN, 37232Nashville, 037232Myung‐Eun Shin - University of Illinois601 S. Goodwin Avenue, Urbana, IL 61801UrbanaIL61807Fei Wang - University of Illinois601 S. Goodwin Avenue, Urbana, IL 61801UrbanaIL61807Heidi E Hamm - Vanderbilt University21st Ave@Pierce Dr., Nashville, TN, 37232NashvilleTN37232
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.21(5), pp.A616-A617
- DOI
- 10.1096/fasebj.21.5.A616-c
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Language
- English
- Date published
- 04/2007
- Academic Unit
- Anatomy and Cell Biology; Iowa Neuroscience Institute; Craniofacial Anomalies Research Center; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984071729802771
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