Elberg G, Rapoport M J, Vashdi-Elberg D, Gertler A, Shechter Y
Department of Hormone Research, The Weizmann Institute of Science, 76100, Rehovot, Israel.
Endocrine. 1996 Feb;4(1):65-71. doi: 10.1007/BF02738876.
Lactogenic hormone-dependent Nb2-11C cells proliferate in response to prolactin (PRL) or human growth hormone (hGH). We have investigated the activation of p21( ras ) and mitogen-activated protein kinase (MAP-kinase) by hGH in lactogen-dependent Nb2-11C and in autonomous hormone-independent Nb2-SP rat lymphoma cells. Exposure of Nb2-11C cells to hGH resulted in a dose-dependent activation of p21( ras ) and of MAP-kinase. Activation occurs at physiological hGH concentration and with a rapid onset (∼1 min) reaching maximal level at 10-20 min. In contrast, in Nb2-SP autonomous lactogen-independent cells, p21( ras ) and MAP-kinase are constitutively activated and a challenge with lactogenic hormone had a modest additional activating effect. TPA, an activator of protein kinase C, enhanced p21( ras ) and MAP-kinase activity in Nb2-11C cells but failed to induce proliferation. The mechanism of activation of p21( ras ) in Nb2-11C cells by lactogenic hormones involves both an increased binding of guanine nucleotides to p21( ras ) as well as an increase in GTP/GDP+GTP ratio. In summary, we have demonstrated here that activation of the p21( ras )/MAP-kinase pathway follows PRL receptor activation but is not sufficient for the lactogenic hormone-dependent mitogenesis.
催乳素依赖性Nb2 - 11C细胞会对催乳素（PRL）或人生长激素（hGH）产生增殖反应。我们研究了hGH对催乳素依赖性Nb2 - 11C细胞和自主性激素非依赖性Nb2 - SP大鼠淋巴瘤细胞中p21(ras)和丝裂原活化蛋白激酶（MAP激酶）的激活作用。将Nb2 - 11C细胞暴露于hGH会导致p21(ras)和MAP激酶呈剂量依赖性激活。在生理浓度的hGH下即可发生激活，且起效迅速（约1分钟），在10 - 20分钟时达到最大水平。相比之下，在Nb2 - SP自主性非催乳素依赖性细胞中，p21(ras)和MAP激酶是组成性激活的，用催乳素进行刺激仅有适度的额外激活作用。佛波酯（TPA）是蛋白激酶C的激活剂，可增强Nb2 - 11C细胞中p21(ras)和MAP激酶的活性，但未能诱导细胞增殖。催乳素在Nb2 - 11C细胞中激活p21(ras)的机制既涉及鸟嘌呤核苷酸与p21(ras)结合的增加，也涉及GTP/GDP + GTP比值的升高。总之，我们在此证明p21(ras)/MAP激酶途径的激活是在PRL受体激活之后，但不足以引起催乳素依赖性的有丝分裂。
