Epidermal growth factor regulates amino acid transport in chick embryo hepatocytes via protein kinase C.
System A-mediated amino acid transport, activation of different steps of signal transduction and involvement of different isoforms of protein kinase C (PKC) have been investigated in chick embryo hepatocytes after epidermal growth factor (EGF) stimulation. EGF rapidly (10 min) increased the rate of aminoisobutyric acid (AIB) uptake in chick embryo hepatocytes freshly isolated on the 19th day of embryonic life, while no change was detectable at other embryonal stages. The growth factor stimulation was abolished by PKC and tyrosine kinase inhibitors and was mimicked by 4-phorbol-12-myristate-13-acetate, dimethyl-2 (PMA). EGF treatment did not modify the phosphorylation of the isoform of phospholipase C (PLC-), and inositol trisphosphate (IP3) and intracellular calcium levels, but it induced an increase in PKC activity. Our data show that EGF regulates amino acid uptake, via PKC and without PLC- activation, only in the last period of chick embryo hepatocyte development. The effects of growth factor on PKC activity suggest the involvement of PKC- and - isoforms in EGF modulation of amino acid transport.
Department of Cellular and Developmental Biology and Department of Experimental Medicine, University 'La Sapienza', P. le A. Moro 5, 00185 Roma, Italy.
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M
Marino
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R
Mele
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Spagnuolo
F M
FM
Pulcinelli
M T
MT
Mangiantini
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Leoni
D000596:Amino Acids / Q000378:metabolism*; D000621:Aminoisobutyric Acids / Q000493:pharmacokinetics; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002642:Chick Embryo; D015536:Down-Regulation; D004815:Epidermal Growth Factor / Q000494:pharmacology / Q000502:physiology*; D007527:Isoenzymes / Q000378:metabolism / Q000502:physiology; D008099:Liver / Q000166:cytology / Q000196:embryology*; D051966:Phospholipase C gamma; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology*; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon; D015290:Second Messenger Systems / Q000187:drug effects; D014018:Tissue Distribution; D010738:Type C Phospholipases / Q000378:metabolism
D000596:Amino Acids; D000621:Aminoisobutyric Acids; D007527:Isoenzymes; D004815:Epidermal Growth Factor; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon; D010738:Type C Phospholipases; D051966:Phospholipase C gamma