PROPERTIES OF PROTEIN-KINASE AND ADENYLATE CYCLASE-DEFICIENT VARIANTS OF A MACROPHAGE-LIKE CELL LINE

PROPERTIES OF PROTEIN-KINASE AND ADENYLATE CYCLASE-DEFICIENT VARIANTS OF A MACROPHAGE-LIKE CELL LINE
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DOI:
10.1002/jcp.1040980114
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发表时间:
1979-01-01
影响因子:
5.6
通讯作者:
ROSEN, OM
ROSEN, OM
中科院分区:
生物学2区
文献类型:
--
作者:
ROSEN, N;PISCITELLO, J;ROSEN, OM

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小鼠巨噬细胞样[肿瘤]细胞系J774.2缺陷的腺苷酸环化酶和蛋白激酶活性的稳定变体,通过克隆细胞耐霍乱毒素和8-溴环[c]AMP(8 Br-cAMP)的生长抑制作用,分别选择。分析这些变体对cAMP介导的吞噬作用增强和cAMP介导的纤溶酶原激活物分泌和生长抑制的响应能力。腺苷酸环化酶的变体不受霍乱毒素的影响,但对8 Br-cAMP介导的纤溶酶原激活剂分泌和生长的抑制敏感。这些变体之一表现出吞噬功能的缺陷,可以通过8 Br-cAMP纠正。蛋白激酶变体表现出正常的基础吞噬作用,不能刺激8溴环腺苷酸或霍乱毒素,他们也不敏感cAMP介导的抑制纤溶酶原激活剂的分泌和生长。cAMP在抑制J774.2生长和纤溶酶原激活物分泌以及增强基础Fc介导的吞噬作用中的3种作用是由cAMP依赖性蛋白激酶介导的。结果支持环核苷酸代谢的变体在理解cAMP对分化细胞功能的调节中的有用性。
Stable variants of the mouse macrophage-like [neoplastic] cell line J774.2 defective in adenylate cyclase and protein kinase activities, were selected by cloning cells resistant to the growth-inhibitory effect of cholera toxin and 8-bromo-cyclic[c]AMP (8 Br-cAMP), respectively. These variants were analyzed for their ability to respond to cAMP-mediated enhancement of phagocytosis and cAMP-mediated inhibition of plasminogen activator secretion and growth. The adenylate cyclase variants were unaffected by cholera toxin but were sensitive to 8 Br-cAMP-mediated inhibition of plasminogen activator secretion and growth. One of these variants exhibited a defect in phagocytosis that could be corrected by 8 Br-cAMP. The protein kinase variants exhibited normal basal phagocytosis that could not be stimulated by 8 Br-cAMP or cholera toxin; they were also insensitive to cAMP-mediated inhibition of plasminogen activator secretion and growth. The 3 effects of cAMP in J774.2.sbd.inhibition of growth and plasminogen activator secretion, and enhancement of basal Fc-mediated phagocytosis.sbd.are mediated by a cAMP-dependent protein kinase. The results support the usefulness of variants in cyclic nucleotide metabolism in understanding the regulation of differentiated cell function by cAMP.