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mTOR, AMPK, and insulin receptor signaling networks in the bovine mammary gland during the lactation cycle
Author(s) -
Bionaz Massimo,
Loor Juan J
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1109-a
Subject(s) - ampk , lactation , pi3k/akt/mtor pathway , insulin receptor , mammary gland , endocrinology , medicine , insulin , chemistry , protein kinase b , microbiology and biotechnology , biology , signal transduction , insulin resistance , protein kinase a , phosphorylation , pregnancy , genetics , breast cancer , cancer
Mammalian cells possess sensory systems that detect energy and metabolic status and adjust flux through metabolic pathways. mTOR ( FRAP1 ) and AMPK signaling pathways control aspects of cellular physiology, transcription, and translation. The activity of both pathways is regulated through integration of many signals, including growth factors, nutrients, and energy availability. To elucidate the role of mTOR and AMPK signaling in mammary we biopsied 6 Holstein cows at ‐15, 1, 15, 30, 60, 120, and 240 days relative to parturition, and isolated RNA for quantitative real‐time RT‐PCR of AKT3 , CSN3 , EIF4E , EIF4EBP1 , FRAP1 , INSR , IRS1 , PDPK1 , PIK3C2A , PRKAA2 , PRKAB1 , RPS6KB1 , and STK11 . Unlike ruminants, these genes have been relatively well‐studied in non‐ruminant cell systems. Lactation increased ( P < 0.05) expression of genes linking insulin ( INSR , IRS1 ) and mTOR signaling ( PDPK1 , AKT3 , FRAP1 , RPS6KB1 , PIK3C2A , and EIF4E ). Expression of these genes increased sharply by day 15 (early lactation) and remained elevated through day 240 (late lactation). IRS1 and CSN3 had similar expression patterns and peaked (4‐ and 40‐fold) on day 60. AMPK‐signaling genes ( PRKAA2 , PRKAB1 , STK11 ) were not affected by stage of lactation, which might improve insulin sensitivity in mammary and prevent down‐regulation of mTOR signaling and protein translation. Network analysis using Ingenuity Pathway Analysis confirmed that FRAP1 and insulin play central roles in cellular and milk protein synthesis. Results indicate that the synthesis of protein in mammary gland is partly regulated through changes in expression of genes with key roles in insulin, mTOR, and AMPK signaling networks.