PMID- 10585492 OWN - NLM STAT- MEDLINE DCOM- 20000113 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 274 IP - 50 DP - 1999 Dec 10 TI - Growth hormone-induced alteration in ErbB-2 phosphorylation status in 3T3-F442A fibroblasts. PG - 36015-24 AB - The growth hormone receptor (GHR), a cytokine receptor superfamily member, requires the JAK2 tyrosine kinase for signaling. We now examine functional interactions between growth hormone (GH) and epidermal growth factor (EGF) in 3T3-F442A fibroblasts. Although EGF enhanced ErbB-2 tyrosine phosphorylation, GH, while causing retardation of its migration on SDS-polyacrylamide gel electrophoresis, decreased ErbB-2's tyrosine phosphorylation. GH-induced retardation was reversed by treatment of anti-ErbB-2 precipitates with both alkaline phosphatase and protein phosphatase 2A, suggesting that GH induced serine/threonine phosphorylation of ErbB-2. Both GH-induced shift in ErbB-2 migration and GH-induced MAP kinase activation were unaffected by a protein kinase C inhibitor but were blocked by the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1 (MEK1) inhibitor, PD98059. Notably, leukemia inhibitory factor, but not interferon-gamma, also promoted ErbB-2 shift and mitogen-activated protein kinase activation. Cotreatment with EGF and GH versus EGF alone resulted in a 35% decline in acute ErbB-2 tyrosine 1248 autophosphorylation, a marked decline (approximately 50%) in DNA synthesis, and substantially decreased cyclin D1 expression. We conclude that in 3T3-F442A cells, 1) the GH-induced decrease in ErbB-2 tyrosine phosphorylation correlates with MEK1/mitogen-activated protein kinase activity and 2) GH antagonizes EGF-induced DNA synthesis and cyclin D1 expression in a pattern consistent with its alteration in ErbB-2 phosphorylation status. FAU - Kim, S O AU - Kim SO AD - Department of Medicine, University of Alabama at Birmingham, AL 35294, USA. FAU - Houtman, J C AU - Houtman JC FAU - Jiang, J AU - Jiang J FAU - Ruppert, J M AU - Ruppert JM FAU - Bertics, P J AU - Bertics PJ FAU - Frank, S J AU - Frank SJ LA - eng GR - CA65686/CA/NCI NIH HHS/United States GR - DK46395/DK/NIDDK NIH HHS/United States GR - GM53271/GM/NIGMS NIH HHS/United States GR - etc. PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Antibodies) RN - 0 (Growth Inhibitors) RN - 0 (Interleukin-6) RN - 0 (LIF protein, human) RN - 0 (Leukemia Inhibitory Factor) RN - 0 (Lif protein, mouse) RN - 0 (Lymphokines) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Recombinant Proteins) RN - 12629-01-5 (Human Growth Hormone) RN - 136601-57-5 (Cyclin D1) RN - 21820-51-9 (Phosphotyrosine) RN - 62229-50-9 (Epidermal Growth Factor) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (Receptor, ErbB-2) RN - EC 2.7.10.2 (JAK2 protein, human) RN - EC 2.7.10.2 (Jak2 protein, mouse) RN - EC 2.7.10.2 (Janus Kinase 2) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 3.1.3.1 (Alkaline Phosphatase) RN - EC 3.1.3.16 (Phosphoprotein Phosphatases) RN - EC 3.1.3.16 (Protein Phosphatase 2) SB - IM MH - 3T3 Cells MH - Alkaline Phosphatase/metabolism MH - Animals MH - Antibodies MH - Cyclin D1/genetics MH - Epidermal Growth Factor/*pharmacology MH - ErbB Receptors/metabolism MH - Gene Expression Regulation/drug effects MH - Growth Inhibitors/pharmacology MH - Human Growth Hormone/*pharmacology MH - Humans MH - *Interleukin-6 MH - Janus Kinase 2 MH - Leukemia Inhibitory Factor MH - Lymphokines/pharmacology MH - Mice MH - Mitogen-Activated Protein Kinases/*metabolism MH - Phosphoprotein Phosphatases/metabolism MH - Phosphorylation MH - Phosphotyrosine/metabolism MH - Protein Phosphatase 2 MH - Protein-Tyrosine Kinases/metabolism MH - *Proto-Oncogene Proteins MH - Receptor, ErbB-2/*metabolism MH - Recombinant Proteins/pharmacology EDAT- 1999/12/10 00:00 MHDA- 1999/12/10 00:01 CRDT- 1999/12/10 00:00 PHST- 1999/12/10 00:00 [pubmed] PHST- 1999/12/10 00:01 [medline] PHST- 1999/12/10 00:00 [entrez] AID - 10.1074/jbc.274.50.36015 [doi] AID - S0021-9258(19)53343-9 [pii] PST - ppublish SO - J Biol Chem. 1999 Dec 10;274(50):36015-24. doi: 10.1074/jbc.274.50.36015.