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PI3K/Akt responses to oxytocin stimulation in Caco2BB gut cells
Author(s) -
Klein Benjamin Y.,
Tamir Hadassah,
Welch Martha G.
Publication year - 2011
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.23243
Subject(s) - pi3k/akt/mtor pathway , oxytocin , protein kinase b , p70 s6 kinase 1 , microbiology and biotechnology , phosphoserine , ribosomal protein s6 , chemistry , biology , phosphorylation , signal transduction , endocrinology , serine
Recently, we discovered oxytocin receptor (OTR) expression in the developing gut villus epithelium that emerges in villus–crypt junctions after weaning. Oxytocin (OT) and OTR regulate many physiological functions in various tissues; however, their function in gut epithelium is unknown. We explored responses of PI3K and Akt phosphoisoforms to OT stimuli in the Caco2BB human gut cell line. In Caco2BB cells, PI3K and pAkt levels peaked at 62.5 nM OT. At higher concentrations, PI3K decreased more gradually than pAkt S473 suggesting that the pAkt S473 response is separate from PI3K. At ≤7.8 nM OT, pAkt T308 increased while pAkt S473 decreased. Using a specific OTR antagonist, we demonstrated that responses of pAkt T308 to OT depend on OTR in contrast to the partial OTR‐dependence of the pAkt S473 response. Differential pAkt phosphoisoform responses included pAkt phosphoserine 473 persistently free of phosphothreonine 308. The reduction in PI3K after 62.5 nM OT for 30 min coincided with OTR internalization. The PI3K/Akt activation profile was somewhat different in other cell lines (MCF‐7 breast cancer cells, HT29 gut cells), which have PI3K activating mutations, that were examined to establish experimental parameters. In Caco2BB cells, the divergent effects of OT upon pAkt phosphoisoforms suggests separate sub‐pathways; pAkt T308 activation depends on OTR via the PI3K pathway and pAkt S473 presumably results from its specific kinase mTORC2 (mammalian target of rapamycin complex 2). Thus, OT may modulate gut cell functions downstream of mTOR complexes (e.g., translation control as suggested by others in uterine cells). We will next explore OT‐stimulated kinase activities downstream of mTOR related to pAkt phosphoisoforms. J. Cell. Biochem. 112: 3216–3226, 2011. © 2011 Wiley Periodicals, Inc.