The G-protein-coupled peptide YY (PYY)/neuropeptide Y Y1 receptor (Y1R) subtype is highly expressed in the proliferative zone of human colonic crypt epithelial cells but biochemical and biological support for growth effects have been lacking. Using a model gut epithelial cell system, we have stably expressed the human Y1R in IEC-6 cells and show that the Y1R does couple to mitogen-activated protein kinase (MAPK) phosphorylation and cell growth. This pathway uses pertussis-toxin-sensitive G-proteins and βγ subunits, inhibited by co-transfected α-transducin. The Src-family tyrosine kinase inhibitor PP1, as well as specific inhibition of the epidermal growth factor receptor tyrosine kinase (EGFR TK) by PD153035, also blocks PYY stimulation of MAPK. This pathway further requires protein kinase C with EGFR TK inhibition blocking PYY-induced protein kinase Cε (PKCε) translocation to the cell membrane. Finally, we show that PYY stimulates growth in Y1R-expressing gut epithelial cells that is dependent on EGFR TK activity. These results demonstrate a novel pathway involving Gi/Go protein, EGFR and PKC to activate MAPK. Further, they support a role for PYY and the Y1R in regulating growth in human colonic epithelium.
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September 2000
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Research Article|
September 08 2000
Peptide YY Y1 receptor activates mitogen-activated protein kinase and proliferation in gut epithelial cells via the epidermal growth factor receptor
Peter J. MANNON;
Peter J. MANNON
1
*Gastroenterology section, Box 3913, Duke University Medical Center, Durham, NC 27710, U.S.A.
†Durham VA, 508 Fulton Street, Durham, NC 27705, U.S.A.
1To whom correspondence should be addressed. Present address: Laboratory of Clinical Investigation, Mucosal Immunity section, NIAID, National Institutes of Health, Building 10, Room 11N238, Bethesda, MD 20892, U.S.A. (e-mail pmannon@niaid.nih.gov).
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Jennifer M. MELE
Jennifer M. MELE
†Durham VA, 508 Fulton Street, Durham, NC 27705, U.S.A.
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Biochem J (2000) 350 (3): 655–661.
Article history
Received:
March 03 2000
Revision Received:
June 05 2000
Accepted:
June 29 2000
Citation
Peter J. MANNON, Jennifer M. MELE; Peptide YY Y1 receptor activates mitogen-activated protein kinase and proliferation in gut epithelial cells via the epidermal growth factor receptor. Biochem J 15 September 2000; 350 (3): 655–661. doi: https://doi.org/10.1042/bj3500655
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