Altered cyclic AMP‐dependent protein kinase activity in a mutant adrenocortical tumor cell line
Altered cyclic AMP‐dependent protein kinase activity in a mutant adrenocortical tumor cell line
复制标题
突变肾上腺皮质肿瘤细胞系中环 AMP 依赖性蛋白激酶活性的改变
DOI：
10.1002/jcp.1040970320
复制
发表时间：
1978
影响因子：
5.6
通讯作者：
B. Schimmer
中科院分区：
文献类型：
--
作者：
N. S. Gutmann;P. A. Rae;B. Schimmer
A somatic cell genetic approach has been used to evaluate the role of cyclic AMP‐dependent protein kinase in ACTH action on adrenal steroidogenesis. A mutant clone, 8BrcAMPr‐1, previously was isolated from an ACTH‐sensitive adrenocortical tumor cell line (clone Y1) following mutagenesis and selective growth in 8‐bromoadenosine 3′, 5′‐monophosphate. This study demonstrates that the 8BrcAMP4‐1 cells have an altered cyclic AMP‐dependent protein kinase. The protein kinase in the cytosol of the mutant characteristically requires, for half‐maximal activity, concentrations of cyclic AMP 7‐fold higher than those required by the enzyme in preparations from the parent. The cytosolic cyclic AMP‐dependent protein kinases of Y1 and 8BrcAMPr‐1 cells chromatograph similarly on columns of DEAE‐cellulose. From each cell line, a major peak of activity (≥ 70% of recovered activity), designated as Peak I, elutes with 0.04–0.06 M NaCl; a second peak of activity, designated as Peak II, elutes with 0.12–0.14 M NaCl. Protein kinase activity in the Peak I fraction of mutant cells has a decreased apparent affinity (4‐fold) for cyclic AMP relative to the corresponding fraction of parental Y1 cells. The protein kinase activities present in Peak II fractions from Y1 and mutant cells are indistinguishable. The protein kinase mutant exhibits poor steroidogenic responses to added ACTH and cyclic AMP; and as shown previously does not display the growth arrest and morphological changes produced in Y1 by these agents. These results suggest that cyclic AMP‐dependent protein kinase is important in the regulation of adrenal steroidogenesis, morphology and growth by ACTH.
