title: The interaction of Gα13 with integrin β1 mediates cell migration by dynamic regulation of RhoA.
abstract: Heterotrimeric G protein Gα13 is known to transmit G protein-coupled receptor (GPCR) signals leading to activation of RhoA and plays a role in cell migration. The mechanism underlying the role of Gα13 in cell migration, however, remains unclear. Recently we found that Gα13 interacts with the cytoplasmic domain of integrin β3 subunits in platelets via a conserved ExE motif. Here we show that a similar direct interaction between Gα13 and the cytoplasmic domain of the integrin β1 subunit plays a critical role in β1-dependent cell migration. Point mutation of either glutamic acid in the Gα13-binding (767)EKE motif in β1 or treatment with a peptide derived from the Gα13-binding sequence of β1 abolished Gα13-β1 interaction and inhibited β1 integrin-dependent cell spreading and migration. We further show that the Gα13-β1 interaction mediates β1 integrin-dependent Src activation and transient RhoA inhibition during initial cell adhesion, which is in contrast to the role of Gα13 in mediating GPCR-dependent RhoA activation. These data indicate that Gα13 plays dynamic roles in both stimulating RhoA via a GPCR pathway and inhibiting RhoA via an integrin signaling pathway. This dynamic regulation of RhoA activity is critical for cell migration on β1 integrin ligands.
authors: Department of Pharmacology, University of Illinois at Chicago, Chicago, IL 60612.
authors: Bo
authors: B
authors: Shen
authors: Department of Pharmacology, University of Illinois at Chicago, Chicago, IL 60612.
authors: Brian
authors: B
authors: Estevez
authors: Department of Pharmacology, University of Illinois at Chicago, Chicago, IL 60612.
authors: Zheng
authors: Z
authors: Xu
authors: Department of Pharmacology, University of Illinois at Chicago, Chicago, IL 60612.
authors: Barry
authors: B
authors: Kreutz
authors: Department of Pharmacology, University of Illinois at Chicago, Chicago, IL 60612.
authors: Andrei
authors: A
authors: Karginov
authors: Department of Pharmacology, University of Illinois at Chicago, Chicago, IL 60612.
authors: Yanyan
authors: Y
authors: Bai
authors: Department of Pharmacology, University of Illinois at Chicago, Chicago, IL 60612 Department of Internal Medicine, Section of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Ohio State University, Columbus, OH 43210.
authors: Feng
authors: F
authors: Qian
authors: Department of Pharmacology, University of Illinois at Chicago, Chicago, IL 60612 Center for Wound Healing and Tissue Regeneration, Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL 60612.
authors: Urao
authors: U
authors: Norifumi
authors: Departments of Biomolecular Chemistry and Medicine, University of Wisconsin-Madison, Madison, WI 53792.
authors: Deane
authors: D
authors: Mosher
authors: Department of Pharmacology, University of Illinois at Chicago, Chicago, IL 60612 xdu@uic.edu.
authors: Xiaoping
authors: X
authors: Du
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion / Q000502:physiology; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000502:physiology*; D003412:Cricetulus; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D015398:Signal Transduction; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D019012:Integrin beta1; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D020742:rhoA GTP-Binding Protein