Cytoskeletal rearrangement and Src and PI-3K-dependent Akt activation control GABA(B)R-mediated chemotaxis

Cellular Signalling
Michelle T BaratiJon B Klein

Abstract

The γ-amino butyric acid (GABA) type B receptors (GABA(B)R) function as chemoattractant receptors in response to GABA(B)R agonists in human neutrophils. The goal of this study was to define signaling mechanisms regulating GABA(B)R-mediated chemotaxis and cytoskeletal rearrangement. In a proteomic study we identified serine/threonine kinase Akt, tyrosine kinases Src and Pyk2, microtubule regulator kinesin and microtubule affinity-regulating kinase (MARK) co-immunoprecipitating with GABA(B)R. To define the contributions of these candidate signaling events in GABA(B)R-mediated chemotaxis, we used rat basophilic leukemic cells (RBL-2H3 cells) stably transfected with human GABA(B1b) and GABA(B2) receptors. The GABA(B)R agonist baclofen induced Akt phosphorylation and chemotaxis by binding to its specific GABA(B)R since pretreatment of cells with CGP52432, a GABA(B)R antagonist, blocked such effects. Moreover, baclofen induced Akt phosphorylation was shown to be dependent upon PI-3K and Src kinases. Baclofen failed to stimulate actin polymerization in suspended RBL cells unless exposed to a baclofen gradient. However, baclofen stimulated both actin and tubulin polymerization in adherent RBL-GABA(B)R cells. Blockade of actin and tubul...Continue Reading

Citations

Jan 7, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Jing WuRui Yang
Jan 7, 2016·Frontiers in Endocrinology·Priscilla Ludovico da SilvaTommaso Simoncini
Apr 16, 2019·The Journal of Clinical Investigation·Taylor S CohenBret R Sellman
Sep 26, 2020·Frontiers in Cellular Neuroscience·Mari Paz Serrano-RegalMaría Victoria Sánchez-Gómez
Jun 22, 2021·Cellular and Molecular Life Sciences : CMLS·Amol K Bhandage, Antonio Barragan

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