The related adhesion focal tyrosine kinase (RAFTK) is tyrosine phosphorylated and participates in colony-stimulating factor-1 macrophage colony-stimulating factor signaling in monocyte-macrophages
The related adhesion focal tyrosine kinase (RAFTK) is tyrosine phosphorylated and participates in colony-stimulating factor-1 macrophage colony-stimulating factor signaling in monocyte-macrophages
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DOI：
10.1182/blood.v91.10.3967.3967_3967_3973
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发表时间：
1998-05-15
期刊：
影响因子：
20.3
通讯作者：
Groopman, JE
中科院分区：
文献类型：
--
作者：
Hatch, WC;Ganju, RK;Groopman, JE
RAFTK是一种新的非受体蛋白激酶，已被证明参与了神经元PC12细胞、巨核细胞、血小板和T细胞的粘着斑信号转导通路。由于局部粘连可能调节细胞骨架功能，从而改变单核巨噬细胞的吞噬、细胞迁移和黏附，我们研究了RAFTK信号在这些细胞中的作用。RAFTK在THP1单核细胞、原代肺泡巨噬细胞和外周血巨噬细胞中大量表达。巨噬细胞集落刺激因子-1/巨噬细胞集落刺激因子(M-CSF)刺激THP1细胞后，RAFTK的酪氨酸磷酸化水平增加，而脂多糖刺激后RAFTK的酪氨酸磷酸化水平也有类似的升高。RAFTK在THP1细胞和外周血巨噬细胞中以相似的动力学被磷酸化。免疫沉淀分析显示RAFTK与信号分子磷脂酰肌醇-3(PI-3)激酶活性有关，PI-3激酶活性也与RAFTK抗体共沉淀，进一步证实了这种相关性，CSF-1/M-CSF受体c-FMS和RAFTK似乎与经CSF-1/M-CSF处理的THP1细胞相关。显性负性激酶突变体对RAFTK的抑制可降低CSF-1/M-CSF诱导的MAPK活性。这些数据表明RAFTK参与了由调节单核巨噬细胞生长和功能的细胞因子CSF-1/M-CSF介导的信号转导通路。(C)1998年由美国血液病学会主办。
RAFTK, a novel nonreceptor protein kinase, has been shown to be involved in focal adhesion signal transduction pathways in neuronal PC12 cells, megakaryocytes, platelets, and T cells. Because focal adhesions may modulate cytoskeletal functions and thereby alter phagocytosis, cell migration, and adhesion in monocyte-macrophages, we investigated the role of RAFTK signaling in these cells. RAFTK was abundantly expressed in THP1 monocytic cells as well as in primary alveolar and peripheral blood-derived macrophages. Colony-stimulating factor-1 (CSF-l)/macrophage colony-stimulating factor (M-CSF) stimulation of THP1 cells increased the tyrosine phosphorylation of RAFTK; similar increases in phosphorylation were also detected after lipopolysaccharide stimulation. RAFTK was phosphorylated with similar kinetics in THP1 cells and peripheral blood-derived macrophages. Immunoprecipitation analysis showed associations between RAFTK and the signaling molecule phosphatidylinositol-3 (PI-3) kinase, PI-3 kinase enzyme activity also coprecipitated with the RAFTK antibody, further confirming this association, The CSF-1/M-CSF receptor c-fms and RAFTK appeared to associate in response to CSF-1/M-CSF treatment of THP1 cells. Inhibition of RAFTK by a dominant-negative kinase mutant reduced CSF-1/M-CSF-induced MAPK activity. These data indicate that RAFTK participates in signal transduction pathways mediated by CSF-1/M-CSF, a cytokine that regulates monocyte-macrophage growth and function. (C) 1998 by The American Society of Hematology.