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Lactogenic hormones rapidly activate p21ras/mitogen-activated protein kinase in Nb2-11C rat lymphoma cells

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Abstract

Lactogenic hormone-dependent Nb2-11C cells proliferate in response to prolactin (PRL) or human growth hormone (hGH). We have investigated the activation of p21ras 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 p21ras 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, p21ras 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 p21ras and MAP-kinase activity in Nb2-11C cells but failed to induce proliferation. The mechanism of activation of p21ras in Nb2-11C cells by lactogenic hormones involves both an increased binding of guanine nucleotides to p21ras as well as an increase in GTP/GDP+GTP ratio. In summary, we have demonstrated here that activation of the p21ras/MAP-kinase pathway follows PRL receptor activation but is not sufficient for the lactogenic hormone-dependent mitogenesis.

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Abbreviations

MAP-kinase:

mitogen-activated protein kinase

PKC:

protein kinase C

hGH:

human growth hormone

bGH:

bovine growth hormone

rGH:

rat growth hormone

oPRL:

ovine prolactin

bPL:

bovine placental lactogen

TPA:

12-0-tetradecanoylphorbol 13-acetate

ECL:

enhanced chemiluminescence

JAK:

janus kinase

ras-GAP:

ras GTPase-activating protein

ras GNRF:

ras guanine nucleotides releasing factor

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Authors and Affiliations

  1. Department of Hormone Research, The Weizmann Institute of Science, 76100, Rehovot, Israel

    Gerard Elberg & Yoram Shechter

  2. Diabetes Unit, Assaf Harofeh Medical Center, Zerifin, Israel

    Micha J. Rapoport

  3. Department of Biochemistry, Food Science and Nutrition, Faculty of Agriculture, The Hebrew University of Jerusalem, Rehovot, Israel

    Dorit Vashdi-Elberg & Arieh Gertler

Authors
  1. Gerard Elberg
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  2. Micha J. Rapoport
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  3. Dorit Vashdi-Elberg
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  4. Arieh Gertler
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  5. Yoram Shechter
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Elberg, G., Rapoport, M.J., Vashdi-Elberg, D. et al. Lactogenic hormones rapidly activate p21ras/mitogen-activated protein kinase in Nb2-11C rat lymphoma cells. Endocr 4, 65–71 (1996). https://doi.org/10.1007/BF02738876

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  • DOI: https://doi.org/10.1007/BF02738876

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