The effects of the normal and oncogenic forms of the neu tyrosine kinase, and the corresponding forms of an immunoglobulin E receptor/neu tyrosine kinase fusion protein, on Xenopus oocyte maturation

Vikram Narasimhan, Owen Hamill, Richard A. Cerione

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4 Citations (Scopus)

Abstract

In this work, we have used Xenopus oocyte maturation as a read-out for examining the ability of the neu tyrosine kinase (p185neu) to participate with the epidermal growth factor (EGF) receptor in a common signal transduction pathway. We find that unlike the case for the EGF receptor, which elicits EGF-dependent maturation of these oocytes as reflected by their germinal vesicle breakdown (GVBD), neither the normal neu tyrosine kinase (p185val664) nor the oncogenic form of neu (p185glu664) are able to effectively trigger this maturation event. However, expression of pl185glu664 causes a specific and significant promotion or the progesterone-induced GVBD, reducing the half-time for this maturation even from 9̃ h to 5̃ h. Stimulation of the progesterone-induccd GVBD did not occur following the expression or a kinase-deficient p185neu protein (in which a lysine residue at position 758 was changed to alanine). Essentially identical results were obtained when the mRNAs coding for fusion proteins comprised or the extracellular domain of the receptor for immunoglobulin E (IgE), and the membrane-spanning and tyrosine kinase domains of normal or oncogenic p185neu (designated IgER/p185val664 and IgER/p185glu664, respectively), were injected into oocytes. Antigen-induced crosslinking of IgER/ p185val164 proteins expressed in oocytes caused a reduction in the half-time for the progesterone-stimulated GVBD from 9̃ to 7̃ h. Thus, the aggregation of the membrane-spanning and/or tyrosine kinase domains of pl185val664 partially mimics the effects of the oncogenic forms of pl185neu. Overall, the results of these studies suggest that the activation of the p185neu tyrosine kinase by a point mutation within its membrane-spanning helix, or an aggregation event, can result in the facilitation of oocyte maturation events that are elicited by other factors (e.g. progesterone). However, the activated p185neu tyrosine kinases are not able to mimic the EGF-stimulated EGF receptor tyrosine kinase in triggering oocyte maturation, which suggests that the EGF receptor and the p185neu tyrosine kinase do not input into identical signal transduction pathways in these cells.

Original languageEnglish (US)
Pages (from-to)164-168
Number of pages5
JournalFEBS Letters
Volume303
Issue number2-3
DOIs
StatePublished - Jun 1 1992
Externally publishedYes

Fingerprint

IgE Receptors
Xenopus
Protein-Tyrosine Kinases
Oocytes
Fusion reactions
Epidermal Growth Factor Receptor
Progesterone
Proteins
Signal transduction
Membranes
Epidermal Growth Factor
Signal Transduction
Agglomeration
Point Mutation
Alanine
Crosslinking
Lysine
Phosphotransferases
Chemical activation
Antigens

Keywords

  • Immunoglobulin E
  • Neu
  • Oncogene
  • Oocyte
  • Tyrosine kinase

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

@article{220271bef2804853a67e5fd00179e518,
title = "The effects of the normal and oncogenic forms of the neu tyrosine kinase, and the corresponding forms of an immunoglobulin E receptor/neu tyrosine kinase fusion protein, on Xenopus oocyte maturation",
abstract = "In this work, we have used Xenopus oocyte maturation as a read-out for examining the ability of the neu tyrosine kinase (p185neu) to participate with the epidermal growth factor (EGF) receptor in a common signal transduction pathway. We find that unlike the case for the EGF receptor, which elicits EGF-dependent maturation of these oocytes as reflected by their germinal vesicle breakdown (GVBD), neither the normal neu tyrosine kinase (p185val664) nor the oncogenic form of neu (p185glu664) are able to effectively trigger this maturation event. However, expression of pl185glu664 causes a specific and significant promotion or the progesterone-induced GVBD, reducing the half-time for this maturation even from 9̃ h to 5̃ h. Stimulation of the progesterone-induccd GVBD did not occur following the expression or a kinase-deficient p185neu protein (in which a lysine residue at position 758 was changed to alanine). Essentially identical results were obtained when the mRNAs coding for fusion proteins comprised or the extracellular domain of the receptor for immunoglobulin E (IgE), and the membrane-spanning and tyrosine kinase domains of normal or oncogenic p185neu (designated IgER/p185val664 and IgER/p185glu664, respectively), were injected into oocytes. Antigen-induced crosslinking of IgER/ p185val164 proteins expressed in oocytes caused a reduction in the half-time for the progesterone-stimulated GVBD from 9̃ to 7̃ h. Thus, the aggregation of the membrane-spanning and/or tyrosine kinase domains of pl185val664 partially mimics the effects of the oncogenic forms of pl185neu. Overall, the results of these studies suggest that the activation of the p185neu tyrosine kinase by a point mutation within its membrane-spanning helix, or an aggregation event, can result in the facilitation of oocyte maturation events that are elicited by other factors (e.g. progesterone). However, the activated p185neu tyrosine kinases are not able to mimic the EGF-stimulated EGF receptor tyrosine kinase in triggering oocyte maturation, which suggests that the EGF receptor and the p185neu tyrosine kinase do not input into identical signal transduction pathways in these cells.",
keywords = "Immunoglobulin E, Neu, Oncogene, Oocyte, Tyrosine kinase",
author = "Vikram Narasimhan and Owen Hamill and Cerione, {Richard A.}",
year = "1992",
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T1 - The effects of the normal and oncogenic forms of the neu tyrosine kinase, and the corresponding forms of an immunoglobulin E receptor/neu tyrosine kinase fusion protein, on Xenopus oocyte maturation

AU - Narasimhan, Vikram

AU - Hamill, Owen

AU - Cerione, Richard A.

PY - 1992/6/1

Y1 - 1992/6/1

N2 - In this work, we have used Xenopus oocyte maturation as a read-out for examining the ability of the neu tyrosine kinase (p185neu) to participate with the epidermal growth factor (EGF) receptor in a common signal transduction pathway. We find that unlike the case for the EGF receptor, which elicits EGF-dependent maturation of these oocytes as reflected by their germinal vesicle breakdown (GVBD), neither the normal neu tyrosine kinase (p185val664) nor the oncogenic form of neu (p185glu664) are able to effectively trigger this maturation event. However, expression of pl185glu664 causes a specific and significant promotion or the progesterone-induced GVBD, reducing the half-time for this maturation even from 9̃ h to 5̃ h. Stimulation of the progesterone-induccd GVBD did not occur following the expression or a kinase-deficient p185neu protein (in which a lysine residue at position 758 was changed to alanine). Essentially identical results were obtained when the mRNAs coding for fusion proteins comprised or the extracellular domain of the receptor for immunoglobulin E (IgE), and the membrane-spanning and tyrosine kinase domains of normal or oncogenic p185neu (designated IgER/p185val664 and IgER/p185glu664, respectively), were injected into oocytes. Antigen-induced crosslinking of IgER/ p185val164 proteins expressed in oocytes caused a reduction in the half-time for the progesterone-stimulated GVBD from 9̃ to 7̃ h. Thus, the aggregation of the membrane-spanning and/or tyrosine kinase domains of pl185val664 partially mimics the effects of the oncogenic forms of pl185neu. Overall, the results of these studies suggest that the activation of the p185neu tyrosine kinase by a point mutation within its membrane-spanning helix, or an aggregation event, can result in the facilitation of oocyte maturation events that are elicited by other factors (e.g. progesterone). However, the activated p185neu tyrosine kinases are not able to mimic the EGF-stimulated EGF receptor tyrosine kinase in triggering oocyte maturation, which suggests that the EGF receptor and the p185neu tyrosine kinase do not input into identical signal transduction pathways in these cells.

AB - In this work, we have used Xenopus oocyte maturation as a read-out for examining the ability of the neu tyrosine kinase (p185neu) to participate with the epidermal growth factor (EGF) receptor in a common signal transduction pathway. We find that unlike the case for the EGF receptor, which elicits EGF-dependent maturation of these oocytes as reflected by their germinal vesicle breakdown (GVBD), neither the normal neu tyrosine kinase (p185val664) nor the oncogenic form of neu (p185glu664) are able to effectively trigger this maturation event. However, expression of pl185glu664 causes a specific and significant promotion or the progesterone-induced GVBD, reducing the half-time for this maturation even from 9̃ h to 5̃ h. Stimulation of the progesterone-induccd GVBD did not occur following the expression or a kinase-deficient p185neu protein (in which a lysine residue at position 758 was changed to alanine). Essentially identical results were obtained when the mRNAs coding for fusion proteins comprised or the extracellular domain of the receptor for immunoglobulin E (IgE), and the membrane-spanning and tyrosine kinase domains of normal or oncogenic p185neu (designated IgER/p185val664 and IgER/p185glu664, respectively), were injected into oocytes. Antigen-induced crosslinking of IgER/ p185val164 proteins expressed in oocytes caused a reduction in the half-time for the progesterone-stimulated GVBD from 9̃ to 7̃ h. Thus, the aggregation of the membrane-spanning and/or tyrosine kinase domains of pl185val664 partially mimics the effects of the oncogenic forms of pl185neu. Overall, the results of these studies suggest that the activation of the p185neu tyrosine kinase by a point mutation within its membrane-spanning helix, or an aggregation event, can result in the facilitation of oocyte maturation events that are elicited by other factors (e.g. progesterone). However, the activated p185neu tyrosine kinases are not able to mimic the EGF-stimulated EGF receptor tyrosine kinase in triggering oocyte maturation, which suggests that the EGF receptor and the p185neu tyrosine kinase do not input into identical signal transduction pathways in these cells.

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