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[The Role of Src-kinase in the Regulation of Endocytosis of EGF-receptor Complexes. I. Dynamics of EGF Internalization, Recycling, Sorting, and Degradation During Inhibition of Src-kinase Activity]

[The Role of Src-kinase in the Regulation of Endocytosis of EGF-receptor Complexes. I. Dynamics of EGF Internalization, Recycling, Sorting, and Degradation During Inhibition of Src-kinase Activity]

N N Zheleznova, M S Melikova, N N Nikol'skiĭ, E S Kornilova

Tsitologiia. 2001;43(12):1136-45.

PMID: 11881152

Abstract:

In the present work, the role of Src-kinase in regulation of different stages of EGF-receptor endocytosis was studied. We used murine fibroblasts with knockout of Src gene and CGP77675, and the inhibitor of Src-family kinases. The absence of Src protein in the cells did not lead to any changes in the rates of 125I-EGF internalization or recycling and caused only slight decrease in the rate of its degradation. At the same time, treatment of the wild type cells with the inhibitor resulted in a small decrease in internalization rate and an increase in recycling. The influence of the inhibitor on 125I-EGF degradation was also more pronounced. But even in this case, the effects were no more than 30% of control values. CGP77675 extended the same effect upon cells of HER14 and HC11 lines. Subcellular fractionation of these cells in Percoll gradient has also demonstrated a slight inhibition of 125I-EGF sorting from early to late endosomes. The more pronounced effect of the Src-family kinase inhibitor on the EGF endocytosis, compared to that of the absence of a single Src protein, suggests a compensating mechanism of the Src-family kinases. A conclusion is made that in spite of a slight influence on practically all stages of intracellular pathway of EGF-receptor complexes, Src-kinases are obviously not the key regulators of their endocytosis.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP234772646	CGP77675		234772-64-6	Price

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