| First Author | Boras M | Year | 2017 |
| Journal | J Exp Med | Volume | 214 |
| Issue | 3 | Pages | 851-874 |
| PubMed ID | 28183734 | Mgi Jnum | J:241223 |
| Mgi Id | MGI:5898169 | Doi | 10.1084/jem.20160647 |
| Citation | Boras M, et al. (2017) Skap2 is required for beta2 integrin-mediated neutrophil recruitment and functions. J Exp Med 214(3):851-874 |
| abstractText | Integrin activation is required for neutrophil functions. Impaired integrin activation on neutrophils is the hallmark of leukocyte adhesion deficiency (LAD) syndrome in humans, characterized by impaired leukocyte recruitment and recurrent infections. The Src kinase-associated phosphoprotein 2 (Skap2) is involved in integrin functions in different leukocyte subtypes. However, the role of Skap2 in beta2 integrin activation and neutrophil recruitment is unknown. In this study, we demonstrate the crucial role of Skap2 in regulating actin polymerization and binding of talin-1 and kindlin-3 to the beta2 integrin cytoplasmic domain, thereby being indispensable for beta2 integrin activation and neutrophil recruitment. The direct interaction of Skap2 with the Wiskott-Aldrich syndrome protein via its SH3 domain is critical for integrin activation and neutrophil recruitment in vivo. Furthermore, Skap2 regulates integrin-mediated outside-in signaling events and neutrophil functions. Thus, Skap2 is essential to activate the beta2 integrins, and loss of Skap2 function is sufficient to cause a LAD-like phenotype in mice. |
