Compartmentalization of PDE-4 and cAMP-dependent protein kinase in neutrophils and macrophages during phagocytosis
Compartmentalization of PDE-4 and cAMP-dependent protein kinase in neutrophils and macrophages during phagocytosis
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吞噬过程中中性粒细胞和巨噬细胞中 PDE-4 和 cAMP 依赖性蛋白激酶的区室化
DOI：
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发表时间：
2007
影响因子：
2.6
通讯作者：
E. Merricks
中科院分区：
文献类型：
--
作者：
K. Pryzwansky;S. Kidao;E. Merricks
在人中性粒细胞吞噬血清调理酶的过程中cAMP的区隔化表明cAMP是调节吞噬作用的重要第二信使。4型cAMP特异性磷酸二酯酶（PDE-4）、cAMP依赖性蛋白激酶（PKA）和腺苷酸环化酶是吞噬细胞中cAMP调控的主要效应分子。免疫荧光显微镜显示，PDE-4亚型（HSPDE-4A, HSPDE-4B, HSPDE-4D）可靶向中性粒细胞中形成的吞噬体，并与PKA和脱颗粒髓过氧化物酶的催化亚基共定位。用福斯克林或罗利普兰提高cAMP水平可抑制PDE-4和PKA在粘附酶散附近的吞噬和积累。在细胞松弛素D处理的细胞中，cAMP、PDE-4和PKA定位于酶酶结合的部位，以抑制吞噬体的形成，这表明酶酶结合Fc/CR3受体触发了吞噬部位cAMP的升高。HSPDE-4A、HSPDE-4B、HSPDE-4D和PKA也定位于单核细胞来源的巨噬细胞形成吞噬体，溶酶体标记CD63显示内化吞噬体周围不存在PDE-4。这些结果表明，cAMP水平在新生吞噬体中受PDE-4的局部调控，PKA可能磷酸化与假足形成和吞噬体内化相关的蛋白。
The compartmentalization of cAMP in human neutrophils during phagocytosis of serum-opsonized zymosan suggests that cAMP is an important second messenger for regulating phagocytosis. Type 4 cAMP-specific phosphodiesterase (PDE-4), cAMP-dependent protein kinase (PKA), and adenylate cyclase are the principal effector molecules for cAMP regulation in phagocytes. Immunofluorescence microscopy demonstrated that PDE-4 isoforms (HSPDE-4A, HSPDE-4B, HSPDE-4D) were targeted to the forming phagosome in neutrophils, and were colocalized with the catalytic subunit of PKA and degranulated myeloperoxidase. Phagocytosis and accumulation of PDE-4 and PKA near adherent zymosan were inhibited by elevating cAMP levels with forskolin or rolipram. cAMP, PDE-4, and PKA were localized at sites of zymosan adherence in cells treated with cytochalasin D to inhibit phagosome formation, suggesting that zymosan engagement to Fc/CR3 receptors triggers cAMP elevations at sites of phagocytosis. HSPDE-4A, HSPDE-4B, HSPDE-4D, and PKA also were localized at the forming phagosome in monocyte-derived macrophages, and the lysosomal marker CD63 demonstrated the absence of PDE-4 around internalized phagolysosomes. These results suggest that cAMP levels are focally regulated by PDE-4 at the nascent phagosome, and that PKA may phosphorylate proteins associated with pseudopodia formation and phagosome internalization.
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环单磷酸鸟苷依赖性蛋白激酶靶向中间丝并磷酸化 A23187 刺激的人中性粒细胞中的波形蛋白。
影响因子：
20.3
作者：
Pryzwansky,KB;Wyatt,TA;Lincoln,TM
通讯作者：
Lincoln,TM
DOI：
--
发表时间：
1982-03
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
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W. Theurkauf;R. Vallee
甲酰肽刺激的中性粒细胞中环 GMP 依赖性蛋白激酶的区室化。
影响因子：
20.3
作者：
Pryzwansky,KB;Wyatt,TA;Nichols,H;Lincoln,TM
通讯作者：
Lincoln,TM
DOI：
10.1016/s0021-9258(18)54851-1
发表时间：
1991-11
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Todd A. Wyatt;Thomas M. Lincoln;K. Pryzwansky
通讯作者：
Todd A. Wyatt;Thomas M. Lincoln;K. Pryzwansky
Fc 受体介导的巨噬细胞吞噬作用期间，Fc γ 受体、p72syk 和桩蛋白的 γ 亚基的酪氨酸磷酸化。
DOI：
--
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Greenberg,S;Chang,P;Silverstein,SC
通讯作者：
Silverstein,SC