Regulation of cell proliferation by epidermal growth factor
- PMID: 6301752
- DOI: 10.3109/10409238309102791
Regulation of cell proliferation by epidermal growth factor
Abstract
Epidermal Growth Factor (EGF) is a 6045 dalton polypeptide which stimulates the proliferation of various cell types in vitro and in vivo. EGF binds to diffusely distributed membrane receptors which rapidly cluster primarily on coated pits areas on the plasma membrane. Subsequently, the EGF-receptor complexes are endocytosed and degraded by lysosomal enzymes. The lateral diffusion coefficient (D) of EGF-receptor complexes on cultured cells increases gradually from D = 2.8 X 10(-10) cm2/sec at 5 degrees C to 8.5 X 10(-10) cm2/sec at 37 degrees C. In the same range of temperature the rotational correlation times change from 25 to 50 microseconds to approximately 350 microseconds. Hence, at 4 degrees C, the occupied EGF receptors translate and rotate rapidly in the plane of the membrane. At 37 degrees C, EGF receptors form microclusters composed of 10 to 50 molecules. Moreover, it is concluded that both at 4 degrees C and 37 degrees C lateral diffusion of the occupied receptors is not the rate determining step for either receptor clustering or internalization. EGF receptor is a 150,000 to 170,000 dalton glycoprotein. The receptor is in close proximity to an EGF-sensitive, cAMP-independent, tyrosine-specific protein kinase which also phosphorylates the receptor molecules itself. The EGF sensitive kinase is similar to the kinase activity which is associated with certain RNA tumor viruses. The fact that the non-mitogenic cyanogen-bromide cleaved EGF is as potent as native EGF in stimulating phosphorylation suggests that EGF-induced, protein phosphorylation is a necessary but insufficient signal for the induction of DNA synthesis by EGF. EGF receptor serves also as the binding site for Transforming Growth Factors (TGF) which compete with EGF and induce anchorage-independent growth of normal cells in soft agar. Tumor promoters such as phorbol ester effect the binding of EGF to its membrane receptors and its ability to stimulate DNA synthesis. EGF itself has also some tumor promoting activity. Hence, the membrane receptor for EGF seems to participate in the regulation of normal and neoplastic growth. Monoclonal antibodies against EGF receptor (IgM) induce various early and delayed effects of EGF, while their monovalent Fab' fragments are devoid of biological activity. These observations support the notions that EGF receptor rather than EGF itself is the active moiety and that the role of the hormone is to perturb the receptor in the appropriate way, probably by inducing the microaggregation of EGF receptors.
Similar articles
-
Protein kinase C phosphorylation of the EGF receptor at a threonine residue close to the cytoplasmic face of the plasma membrane.Nature. 1984 Oct 4-10;311(5985):480-3. doi: 10.1038/311480a0. Nature. 1984. PMID: 6090944
-
Biological role of epidermal growth factor-receptor clustering. Investigation with monoclonal anti-receptor antibodies.J Biol Chem. 1983 Jan 25;258(2):846-53. J Biol Chem. 1983. PMID: 6296087
-
Epidermal growth factor, but not nerve growth factor, stimulates tyrosine-specific protein-kinase activity in pheochromocytoma (PC12) plasma membranes.Biochimie. 1985 Oct-Nov;67(10-11):1177-83. doi: 10.1016/s0300-9084(85)80117-6. Biochimie. 1985. PMID: 3000461
-
[Epidermal growth factor: structure, location, phosphorylation and regulation of its receptor].Biochimie. 1984 Jul-Aug;66(7-8):515-30. doi: 10.1016/0300-9084(84)90146-9. Biochimie. 1984. PMID: 6099148 Review. French.
-
The biochemistry and physiology of the receptor-kinase for epidermal growth factor.Mol Cell Endocrinol. 1983 Jul;31(1):1-19. doi: 10.1016/0303-7207(83)90027-8. Mol Cell Endocrinol. 1983. PMID: 6309581 Review.
Cited by
-
Domain deletion in the extracellular portion of the EGF-receptor reduces ligand binding and impairs cell surface expression.Cell Regul. 1990 Jan;1(2):173-88. doi: 10.1091/mbc.1.2.173. Cell Regul. 1990. PMID: 2100196 Free PMC article.
-
Epidermal growth factor is synergistic with phorbol esters and vasopressin in stimulating arachidonate release and prostaglandin production in renal glomerular mesangial cells.Biochem J. 1988 Jan 15;249(2):587-92. doi: 10.1042/bj2490587. Biochem J. 1988. PMID: 3124830 Free PMC article.
-
Biological activities of EGF-receptor mutants with individually altered autophosphorylation sites.EMBO J. 1988 Oct;7(10):3045-52. doi: 10.1002/j.1460-2075.1988.tb03169.x. EMBO J. 1988. PMID: 3263271 Free PMC article.
-
An insertional mutant of epidermal growth factor receptor allows dissection of diverse receptor functions.EMBO J. 1987 Sep;6(9):2669-76. doi: 10.1002/j.1460-2075.1987.tb02558.x. EMBO J. 1987. PMID: 2824188 Free PMC article.
-
Cytosine arabinoside increases the binding of 125I-labelled epidermal growth factor and 125I-transferrin and enhances the in vitro targeting of human tumour cells with anti-(growth factor receptor) mAb.Cancer Immunol Immunother. 1993 Aug;37(3):150-6. doi: 10.1007/BF01525428. Cancer Immunol Immunother. 1993. PMID: 8392910 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Other Literature Sources