Regulation of luteinizing hormone-releasing hormone receptor binding by heterologous and autologous receptor-stimulated tyrosine phosphorylation

C. Liebow, M. T. Lee, A. R. Kamer, A. V. Schally

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Pancreatic cancers overexpress tyrosine kinase and luteinizing hormone-releasing hormone (LH-RH) receptor (LH-RHR)-mediated tyrosine phosphatase. LH-RHR is a 60-kDa protein. One of the substrates of epidermal growth factor (EGF)-stimulated tyrosine kinase activity and LH-RH-and somatostatin-stimulated tyrosine phosphatase activity is also a 60-kDa protein. This suggests the possibility that LH-RHR regulation by tyrosine phosphatase and tyrosine kinase is mediated by (de)phosphorylation of existing LH-RHR. To test this hypothesis, membranes of MIA PaCa-2 cells, a human dedifferentiated pancreatic cancer cell line, were incubated without hormone (control) or with 0.1 μM EGF or somatostatin analogue RC-160 for 1 hr at 4°C to phosphorylate the 60-kDa protein. Competition binding experiments with I125-labeled [D-Trp6]LH-RH by displacement with a nonradioactive ligand showed that the LH-RH binding in 69% of the points was increased by EGF and 85% was decreased by RC-160 compared with controls (n = 61; both significant, P < 0.001). The specific binding was altered, increasing 50-150% after preincubation with EGF and decreasing 60-70% after RC-160. No change was seen in the binding affinity constant after pretreatment with EGF or RC-160. This shows that phosphorylation regulates binding of LH-RH and may explain the up-regulation by EGF and down-regulation by RC-160 and by LH-RH of the LH-RH response.

Original languageEnglish (US)
Pages (from-to)2244-2248
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number6
DOIs
StatePublished - Jan 1 1991
Externally publishedYes

Keywords

  • Epidermal growth factor
  • Oncogenes and anti-oncogenes
  • Pancreatic cancer
  • Somatostatin
  • Tyrosine kinase and phosphatase

ASJC Scopus subject areas

  • General
  • Genetics

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