Transmembrane delivery of polypeptide growth factors bypassing the intrinsic cell surface receptors: synthesis and biological activity of a conjugate of epidermal growth factor with alpha 2-macroglobulin.

Abstract:

:Epidermal growth factor (EGF) was derivatized at the amino terminus with N-succinimidyl 3-(2-pyridyldithio)propionate and then cross-linked to the cysteinyl residues of alpha 2-macroglobulin (alpha 2M) via disulfide bonds. The EGF-alpha 2M conjugate delivered EGF into dense lysosomal fractions through binding to alpha 2M receptors in a variant of mouse Swiss/3T3 fibroblasts, NR-6, which are deficient in EGF receptors. The conjugate stimulated DNA synthesis in Swiss/3T3 cells, but it did not stimulate DNA synthesis in NR-6 cells. This differential stimulation was due to the conjugate's binding to EGF receptors since bacitracin, which completely inhibits [125I]alpha 2M binding to its receptors, inhibited conjugate binding by approximately 80%. Thus, EGF bound to and internalized through alpha 2M receptors does not function as a mediator for DNA stimulation. The mechanisms of action of the conjugate are discussed in relation to the role of receptor-mediated endocytic pathways.

journal_name

Cell Struct Funct

authors

Ito F,Ito S,Shimizu N

doi

10.1247/csf.9.105

subject

Has Abstract

pub_date

1984-06-01 00:00:00

pages

105-15

issue

2

eissn

0386-7196

issn

1347-3700

journal_volume

9

pub_type

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