Protamine enhances epidermal growth factor (EGF)-stimulated mitogenesis by increasing cell surface EGF receptor number. Implications for existence of cryptic EGF receptors

V. B. Lokeshwar, S. S. Huang, J. S. Huang

Research output: Contribution to journalArticle

20 Scopus citations


Treatment of Swiss mouse 3T3 cells and human epidermoid carcinoma A431 cells with protamine at 37°C increased the 125I-epidermal growth factor (EGF) binding activity at 4°C. The effect of protamine on the increase of 125-EGF binding activity appeared to be time, temperature, and dose dependent. This up-modulation of 125I-EGF binding by protamine correlated with protamine enhancement of EGF-stimulated mitogenesis, with respect to the magnitude of the effect and the dose response curves. Scatchard plot analyses indicated that protamine induced an increase in numbers of both high and low affinity EGF receptors without affecting their affinities. Protamine also increased functionally active EGF receptors in plasma membranes and solubilized membranes. This was evidenced by Scatchard plot analyses and by a protamine-induced increase of 125I-EGF-EGF receptor complex and an increase in EGF-stimulated phosphorylation of the EGF receptor. Combined with column chromatography of the solubilized EGF receptor on protamine-agarose gel, these results suggest that protamine may increase the EGF receptor number by directly activating cryptic EGF receptors in the plasma membrane.

Original languageEnglish (US)
Pages (from-to)19318-19326
Number of pages9
JournalJournal of Biological Chemistry
Issue number32
StatePublished - Dec 1 1989


ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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