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Two Forms of the Heparin-binding EGF-like Growth Factor Precursor, a Receptor for Diphtheria Toxin

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Abstract

A new mRNA coding for the heparin-binding EGF-like growth factor (HB-EGF) was found in Vero cells. The corresponding cDNA had C-156 in place of T, which resulted in a loss of the NheI site and replacement of Leu-33 with Pro in the HB-EGF precursor. The known and new forms of the precursor were accordingly termed L and P. A conformational change in the corresponding propeptide region was assumed to affect the processing of soluble secreted HB-EGF. The L and P mRNAs are differently expressed in various cell lines, have identical 5"-untranslated sequences, and are probably transcribed from one promoter and then alternatively spliced. Stimulation of resting Vero cells with tetraphorbol ester (TPA) substantially increased the production of the L form, decreased the production of the P form, and did not affect the expression of total HB-EGF mRNA. This was associated with increased binding of the diphtheria toxin, suggesting that the L HB-EGF precursor acts as its receptor.

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Authors and Affiliations

  1. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 117984, Russia

    E. V. Loukianov & Yu. V. Kozlov

  2. Center for Medical Studies, The University of Oslo, Moscow, 117334, Russia

    E. V. Loukianov & Yu. V. Kozlov

  3. Institute of Cancer Research, Norwegian Radium Hospital, Oslo, 0310, Norway

    E. V. Loukianov, A. Wiedlocha & S. Olsnes

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  1. E. V. Loukianov
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  2. A. Wiedlocha
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  3. S. Olsnes
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  4. Yu. V. Kozlov
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Loukianov, E.V., Wiedlocha, A., Olsnes, S. et al. Two Forms of the Heparin-binding EGF-like Growth Factor Precursor, a Receptor for Diphtheria Toxin. Molecular Biology 35, 122–129 (2001). https://doi.org/10.1023/A:1004819321876

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