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Pretranslational and posttranslational regulation of the EGF receptor during the prereplicative phase of liver regeneration

✍ Scribed by Staffan Johansson; Niclas Andersson; Göran Andersson

Publisher
John Wiley and Sons
Year
1990
Tongue
English
Weight
975 KB
Volume
12
Category
Article
ISSN
0270-9139

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✦ Synopsis

W e studied the regulation of the epidermal growth factor receptor mRNA and the number of epidermal growth factor binding sites in subcellular compartmenta involved in the bioeyntheeis and endocytoeis of the epidermal growth factor receptor during the prereplicative phaee of liver regeneration. The epidermal growth factor receptor mRNA, quantified by solution hybridization, decreased after partial hepatectomy, with a nadir of about 36% 18 hr after hepatectomy. A n even stronger decrease in the number of epidermal growth factor binding eitem after partial hepatectomy was obrved in a Gold-enriched low-deneity membrane fraction, reflecting available newly synthesized epidermal growth factor receptors. It im mggeded that this decrease in newly eyntheeized available epidermal growth factor receptors is c a d primarily, but not entirely, by decreased epidermal growth factor receptor mRNA levels and the additional downregulation of epidermal growth factor binding sitem may involve poettranslational mechaniamn such ae intracellular occupation by t r d o r m i n g growth factors.

The observation that the number of specific epidermal growth factor binding sites after partial hepatectomy wae only moderately r e d u d in prelyaosomal endosomea and in lysosomes, compared with the newly syntheeieed receptors, may indicate that a pool of receptors targeted for lyeoeomes esimta and these receptors are regulated in a different manner than the receptor pool W t e d for the cell surface.

Furthermore, at least two separable endocytic subcompartmenta are involved in the transport of the epidermal growth factor/epidermal gmwkh factor receptor complex in the liver. The complex 5ret enters early endommeas, then enters late, prelymaomal endosomes, where the epidermal growth factor is proteolyt-

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