title: Polyamine-dependent activation of Rac1 is stimulated by focal adhesion-mediated Tiam1 activation.
abstract: Integrin receptors cluster on the cell surface and bind to extra cellular matrix (ECM) proteins triggering the formation of focal contacts and the activation of various signal transduction pathways that affect the morphology, motility, gene expression and survival of adherent cells. Polyamine depletion prevents the increase in autophosphorylation of focal adhesion kinase (FAK) and Src during attachment. Rac activity also shows a steady decline, and its upstream guanine nucleotide exchange factor (GEF), Tiam1 also shows a reduction in total protein level when cells are depleted of polyamines. When Tiam1 and Rac1 interaction was inhibited by NSC-23766, there was not only a decrease in Rac1 activity as expected but also a decrease in FAK auto-phosphorylation. Inhibition of Src activity by PP2 also reduced FAK autophosphorylation, which implies that Src modulates FAK autophosphorylation. From the data obtained in this study we conclude that FAK and Src are rapidly activated upon fibronectin mediated signaling leading to Tiam1-mediated Rac1 activation and that intracellular polyamines influence the signaling strength by modulating interaction of Src with Tiam1 using focal adhesion kinase as a scaffolding site.
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Bertha C
authors.initials: BC
authors.lastname: Elias
authors.forename: Sujoy
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: Ramesh M
authors.initials: RM
authors.lastname: Ray
authors.forename: Leonard R
authors.initials: LR
authors.lastname: Johnson
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000494:pharmacology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D022001:Focal Adhesions / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D008954:Models, Biological; D009842:Oligopeptides / Q000494:pharmacology; D011073:Polyamines / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D005353:Fibronectins; D020662:Guanine Nucleotide Exchange Factors; D009842:Oligopeptides; D011073:Polyamines; C046617:arginyl-glycyl-aspartyl-serine; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases; D020830:rac1 GTP-Binding Protein
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