Regulation of lamellipodial persistence, adhesion turnover, and motility in macrophages by focal adhesion kinase.
Regulation of lamellipodial persistence, adhesion turnover, and motility in macrophages by focal adhesion kinase.
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DOI：
10.1083/jcb.200708093
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发表时间：
2007-12-17
期刊：
影响因子：
--
通讯作者：
Bouton AH
中科院分区：
文献类型：
--
作者：
Owen KA;Pixley FJ;Thomas KS;Vicente-Manzanares M;Ray BJ;Horwitz AF;Parsons JT;Beggs HE;Stanley ER;Bouton AH
巨噬细胞是先天免疫系统的关键组成部分。在这项研究中，我们研究了粘着斑激酶（FAK）和相关激酶Pyk2如何整合粘附信号和生长因子受体信号来调节不同的巨噬细胞功能。从FAK有条件地从髓系细胞中删除的小鼠中分离的原代骨髓巨噬细胞表现出升高的趋化活性、改变的粘附动力学、受损的趋化性、升高的基础Rac 1活性和明显不能形成定向运动所必需的稳定板状伪足。FAK在体外对巨噬细胞功能的贡献在体内得到证实，这一发现表明，在FAK不存在的情况下，单核细胞向炎症部位的募集受到损害。原代巨噬细胞中Pyk2表达的降低也导致侵袭能力的降低。然而，FAK和Pyk2的联合损失没有比单独损失任何一种分子更大的影响，表明两种激酶在相同的途径中起作用以促进侵袭。
Macrophages are a key component of the innate immune system. In this study, we investigate how focal adhesion kinase (FAK) and the related kinase Pyk2 integrate adhesion signaling and growth factor receptor signaling to regulate diverse macrophage functions. Primary bone marrow macrophages isolated from mice in which FAK is conditionally deleted from cells of the myeloid lineage exhibited elevated protrusive activity, altered adhesion dynamics, impaired chemotaxis, elevated basal Rac1 activity, and a marked inability to form stable lamellipodia necessary for directional locomotion. The contribution of FAK to macrophage function in vitro was substantiated in vivo by the finding that recruitment of monocytes to sites of inflammation was impaired in the absence of FAK. Decreased Pyk2 expression in primary macrophages also resulted in a diminution of invasive capacity. However, the combined loss of FAK and Pyk2 had no greater effect than the loss of either molecule alone, indicating that both kinases function within the same pathway to promote invasion.
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影响因子：
4
作者：
Pixley, FJ;Xiong, Y;Ye, BH
通讯作者：
Ye, BH
DOI：
10.1083/jcb.126.6.1585
发表时间：
1994-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Lin TH;Yurochko A;Kornberg L;Morris J;Walker JJ;Haskill S;Juliano RL
通讯作者：
Juliano RL
影响因子：
3
作者：
Clausen, BE;Burkhardt, C;Förster, I
通讯作者：
Förster, I
DOI：
10.1073/pnas.1834348100
发表时间：
2003-09-16
影响因子：
11.1
作者：
Okigaki, M;Davis, C;Schlessinger, J
通讯作者：
Schlessinger, J
影响因子：
158.5
作者：
Miller, DH;Khan, OA;O'Connor, PW
通讯作者：
O'Connor, PW