Akt2 is required for macrophage chemotaxis.
Tumor-associated macrophages play an important role in tumorigenesis and metastasis. Trafficking of macrophages to the proximity of tumors is mediated by CSF-1, a growth factor. In this study, we investigated the role of PKB/Akt in CSF-1-induced macrophage migration. Disruption of Akt2 expression by small interference RNA impaired chemotaxis of both THP-1 cells and mouse peritoneal macrophages. Phosphorylation of PKCzeta, an essential component in chemotaxis signaling pathway, was reduced. LIMK/Cofilin, downstream of PKCzeta, regulated cytoskeleton rearrangement during cell migration. Disruption of Akt2 expression inhibited CSF-1-induced LIMK/Cofilin phosphorylation, which contributed to defects in actin polymerization and chemotaxis. Furthermore, MCP-1, a chemokine, -induced macrophage chemotaxis was also impaired. Taken together, our results demonstrated that Akt2 plays an essential role in both CSF-1- and chemokine-induced chemotaxis of macrophages.
Zhang
Baogang
B
Cancer Institute and Hospital, Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, PR China.
Ma
Yongjie
Y
Guo
Hua
H
Sun
Baocun
B
Niu
Ruifang
R
Ying
Guoguang
G
Zhang
Ning
N
D051339:Actin Depolymerizing Factors / Q000276:immunology / Q000378:metabolism; D000199:Actins / Q000276:immunology / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D018932:Chemokine CCL2 / Q000276:immunology* / Q000378:metabolism; D002633:Chemotaxis / Q000235:genetics / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology; D006801:Humans; D054461:Lim Kinases / Q000276:immunology / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000276:immunology*; D034741:RNA, Small Interfering / Q000235:genetics
D051339:Actin Depolymerizing Factors; D000199:Actins; D018932:Chemokine CCL2; D034741:RNA, Small Interfering; D016173:Macrophage Colony-Stimulating Factor; C494921:AKT2 protein, human; C494922:Akt2 protein, mouse; D054461:Lim Kinases; D051057:Proto-Oncogene Proteins c-akt