Lactogenic hormones rapidly activate p21 ras /mitogen-activated protein kinase in Nb2-11C rat lymphoma cells

Autor: Dorit Vashdi-Elberg, Micha J. Rapoport, Arieh Gertler, Yoram Shechter, Gerard Elberg
Rok vydání: 1996
Předmět:
Zdroj: Endocrine. 4:65-71
ISSN: 1559-0100
1355-008X
DOI: 10.1007/bf02738876
Popis: 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.
Databáze: OpenAIRE