Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.12857/115160
Title: The tyrosine kinase Abl is a component of macrophage podosomes and is required for podosome formation and function
Authors: Baruzzi, Anna 
Berton, Giorgio 
Keywords: Abl;Cell migration;Macrophage;Podosome;Signal transduction
Keywords Plus: 3-DIMENSIONAL MIGRATION;FAMILY KINASES;C-ABL;INHIBITION;CORTACTIN
Mesh headings: Cell Surface Extensions;Macrophages;Oncogene Proteins v-abl;Protein-Tyrosine Kinases
Secondary Mesh headings: Actins;Animals;Benzamides;Cell Movement;Cells, Cultured;Humans;Imatinib Mesylate;Mice;Mice, Inbred C57BL;Piperazines;Protein Kinase Inhibitors;Pyrimidines;RNA, Small Interfering
Issue Date: Oct-2012
Publisher: WILEY
Journal: European journal of immunology 
Abstract: 
Myeloid leukocytes form actin-based plasma membrane protrusions, called podosomes, that are implicated in myeloid cell recruitment into tissues and cell migration within the interstitium. In this study, we show that tyrosine kinases of the Abl family are present in podosomes formed by murine and human macrophages. Silencing of Abl expression in bone marrow-derived macrophages and monocyte-derived macrophages by siRNA or Abl enzymatic inhibition with imatinib resulted in the disassembly of macrophage podosomes and the reduction of their capacity to degrade an extracellular matrix and migrate through matrigel matrices and endothelial cell monolayers. Additionally, macrophages deficient in Src-family kinases, which cross-talk with Abl in regulating macrophage migration, also demonstrated podosome disassembly. These findings suggest that podosome disassembly induced by Abl targeting may inhibit podosome-dependent functions such as leukocyte recruitment into inflammatory sites and osteoclast-dependent bone resorption.
URI: http://hdl.handle.net/20.500.12857/115160
ISSN: 00142980
DOI: 10.1002/eji.201142270
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