| First Author | Abshire MY | Year | 2011 |
| Journal | J Leukoc Biol | Volume | 89 |
| Issue | 2 | Pages | 251-7 |
| PubMed ID | 21084629 | Mgi Jnum | J:168496 |
| Mgi Id | MGI:4888453 | Doi | 10.1189/jlb.0710395 |
| Citation | Abshire MY, et al. (2011) Macrophage motility requires distinct {alpha}5{beta}1/FAK and {alpha}4{beta}1/paxillin signaling events. J Leukoc Biol 89(2):251-7 |
| abstractText | Macrophages function as key inflammatory mediators at sites of infection and tissue damage. Integrin and growth factor receptors facilitate recruitment of monocytes/macrophages to sites of inflammation in response to numerous extracellular stimuli. We have shown recently that FAK plays a role in regulating macrophage chemotaxis and invasion. As FAK is an established downstream mediator of integrin signaling, we sought to define the molecular circuitry involving FAK and the predominant beta1 integrin heterodimers expressed in these cells-alpha4beta1 and alpha5beta1. We show that alpha4beta1 and alpha5beta1 integrins are required for efficient haptotactic and chemotactic invasion and that stimulation of these integrin receptors leads to the adoption of distinct morphologies associated with motility. FAK is required downstream of alpha5beta1 for haptotaxis toward FN and chemotaxis toward M-CSF-1 and downstream of alpha4beta1 for the adoption of a polarized phenotype. The scaffolding molecule paxillin functions independently of FAK to promote chemotaxis downstream of alpha4beta1. These studies expand our understanding of beta1 integrin signaling networks that regulate motility and invasion in macrophages and thus, provide important new insights into mechanisms by which macrophages perform their diverse functions. |
