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Epidermal growth factor inhibits 14 C‐α‐methyl‐ d ‐glucopyranoside uptake in renal proximal tubule cells: Involvement of PLC/PKC, p44/42 MAPK, and cPLA 2
Author(s) -
Jae Han Ho,
Yeong Park Ji,
Jung Lee Yun,
Taub Mary
Publication year - 2004
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.10438
Subject(s) - protein kinase c , epidermal growth factor , staurosporine , mapk/erk pathway , endocrinology , phospholipase c , medicine , wortmannin , chemistry , biology , kinase , signal transduction , receptor , microbiology and biotechnology , biochemistry , protein kinase b
The effect of EGF on 14 C‐α‐methyl‐ d ‐glucopyranoside (α‐MG) uptake and its related signaling pathways were examined in primary cultured rabbit renal proximal tubule cells (PTCs). Epidermal growth factor (EGF) (50 ng/ml) was found to inhibit α‐MG uptake, a distinctive proximal tubule marker. The EGF effect was blocked by AG1478 (an EGF receptor antagonist) or genistein and herbimycin (tyrosine kinase inhibitors), respectively. In addition, the EGF‐induced inhibition of α‐MG uptake was blocked by neomycin and U73122 (phospholipase C inhibitors) as well as staurosporine, H‐7, and bisindolylmaleimide I (protein kinase C inhibitors). EGF was also observed to increase inositol phosphate formation. Furthermore, both the EGF‐induced inhibition of α‐MG uptake and increase of arachidonic acid (AA) release were blocked by AACOCF 3 (a cytosolic phospholipase A 2 inhibitor), indomethacin (a cyclooxygenase inhibitor), and econazole (a cytochrome P‐450 epoxygenase inhibitor). We examined the involvement of mitogen‐activated protein kinases (MAPKs) in mediating the effect of EGF on α‐MG uptake. Indeed, EGF increased phosphorylation of p44/p42 MAPK and the EGF‐induced inhibition of α‐MG uptake as well as the stimulatory effect of EGF on AA release was blocked by PD 98059 (a p44/42 MAPK inhibitor), suggesting a causal relationship. However, inhibitors of PKC also prevented the EGF‐induced increase of AA release. In conclusion, EGF partially inhibited α‐MG uptake via PLC/PKC, p44/42 MAPK, and PLA 2 signaling pathways. J. Cell. Physiol. 199: 206–216, 2004© 2003 Wiley‐Liss, Inc.