title: Lactogenic hormones rapidly activate p21( ras )/mitogen-activated protein kinase in Nb2-11C rat lymphoma cells.
abstract: 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.
authors.affiliation: Department of Hormone Research, The Weizmann Institute of Science, 76100, Rehovot, Israel.
authors.forename: G
authors.initials: G
authors.lastname: Elberg
authors.forename: M J
authors.initials: MJ
authors.lastname: Rapoport
authors.forename: D
authors.initials: D
authors.lastname: Vashdi-Elberg
authors.forename: A
authors.initials: A
authors.lastname: Gertler
authors.forename: Y
authors.initials: Y
authors.lastname: Shechter