title: Protein tyrosine phosphatase-PEST and β8 integrin regulate spatiotemporal patterns of RhoGDI1 activation in migrating cells.
abstract: Directional cell motility is essential for normal development and physiology, although how motile cells spatiotemporally activate signaling events remains largely unknown. Here, we have characterized an adhesion and signaling unit comprised of protein tyrosine phosphatase (PTP)-PEST and the extracellular matrix (ECM) adhesion receptor β8 integrin that plays essential roles in directional cell motility. β8 integrin and PTP-PEST form protein complexes at the leading edge of migrating cells and balance patterns of Rac1 and Cdc42 signaling by controlling the subcellular localization and phosphorylation status of Rho GDP dissociation inhibitor 1 (RhoGDI1). Translocation of Src-phosphorylated RhoGDI1 to the cell's leading edge promotes local activation of Rac1 and Cdc42, whereas dephosphorylation of RhoGDI1 by integrin-bound PTP-PEST promotes RhoGDI1 release from the membrane and sequestration of inactive Rac1/Cdc42 in the cytoplasm. Collectively, these data reveal a finely tuned regulatory mechanism for controlling signaling events at the leading edge of directionally migrating cells.
authors: Department of Neurosurgery, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors: Hye Shin
authors: HS
authors: Lee
authors: Department of Neurosurgery, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors: Mujeeburahiman
authors: M
authors: Cheerathodi
authors: College of Veterinary Medicine, Texas A&M University, College Station, Texas, USA.
authors: Sankar P
authors: SP
authors: Chaki
authors: Department of Neurosurgery, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors: Steve B
authors: SB
authors: Reyes
authors: Department of Neuro-Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors: Yanhua
authors: Y
authors: Zheng
authors: Department of Neuro-Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors: Zhimin
authors: Z
authors: Lu
authors: Université de Lyon, Lyon, France.
authors: Helena
authors: H
authors: Paidassi
authors: Department of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, California, USA.
authors: Celine
authors: C
authors: DerMardirossian
authors: The Benaroya Research Institute, Seattle, Washington, USA.
authors: Adam
authors: A
authors: Lacy-Hulbert
authors: College of Veterinary Medicine, Texas A&M University, College Station, Texas, USA.
authors: Gonzalo M
authors: GM
authors: Rivera
authors: Department of Neurosurgery, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA jhmccarty@mdanderson.org.
authors: Joseph H
authors: JH
authors: McCarty
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D044783:F-Box Proteins / Q000378:metabolism; D000073979:F-Box-WD Repeat-Containing Protein 7; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D039641:Integrin beta Chains / Q000378:metabolism*; D008297:Male; D051379:Mice; D010766:Phosphorylation; D011485:Protein Binding; D060066:Protein Interaction Maps; D054594:Protein Tyrosine Phosphatase, Non-Receptor Type 12 / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D062948:rho Guanine Nucleotide Dissociation Inhibitor alpha / Q000378:metabolism*
chemical_list: D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513272:Fbxw7 protein, mouse; D039641:Integrin beta Chains; C094865:integrin beta8; D062948:rho Guanine Nucleotide Dissociation Inhibitor alpha; D044767:Ubiquitin-Protein Ligases; D054594:Protein Tyrosine Phosphatase, Non-Receptor Type 12; C516739:Ptpn12 protein, mouse; D020830:rac1 GTP-Binding Protein