Journal article
Growth Hormone-induced Alteration in ErbB-2 Phosphorylation Status in 3T3-F442A Fibroblasts
The Journal of biological chemistry, Vol.274(50), pp.36015-36024
12/1999
DOI: 10.1074/jbc.274.50.36015
PMID: 10585492
Abstract
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-γ, 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.
Details
- Title: Subtitle
- Growth Hormone-induced Alteration in ErbB-2 Phosphorylation Status in 3T3-F442A Fibroblasts
- Creators
- Sung-Oh KimJon C.D HoutmanJing JiangJ. Michael RuppertPaul J BerticsStuart J Frank
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.274(50), pp.36015-36024
- DOI
- 10.1074/jbc.274.50.36015
- PMID
- 10585492
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Language
- English
- Date published
- 12/1999
- Academic Unit
- Microbiology and Immunology; Internal Medicine
- Record Identifier
- 9984094719802771
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