Study summary · research use only
IGF-I and vasoactive intestinal peptide (VIP) regulate cAMP-response element-binding protein (CREB)-dependent transcription via the mitogen-activated protein kinase (MAPK) pathway in pituitary cells: requirement of Rap1
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
In this study of cultured male rat pituitary cells, the authors examined how insulin-like growth factor I (IGF-I) and vasoactive intestinal peptide (VIP) regulate CREB-dependent transcription. They report that IGF-I or VIP (10(-7) M) stimulated the MAPK cascade, that VIP-dependent ERK activation required PKA-Rap1 signaling (reduced by Rap1 GAP1), and that IGF-I phosphorylated CREB through the Ras-MAPK pathway while VIP phosphorylated CREB directly via PKA. Using GH4C1 cells transfected with a CRE reporter, IGF-I and VIP stimulation of CRE-mediated transcription required both Ras-MAPK and cAMP/PKA signaling and was blocked by Rap1 GAP1. The authors suggest IGF-I- and VIP-induced lactotroph proliferation may involve Rap1.
Abstract
In previous studies we demonstrated that vasoactive intestinal peptide (VIP) mediation, and interactions between mitogen-activated protein kinase (MAPK) and cAMP/protein kinase A (PKA) signaling pathways are implicated in insulin-like growth factor I (IGF-I)- and VIP-induced lactotroph proliferation. These facts led us to investigate the intracellular mechanisms involved in IGF-I- and VIP-induced lactotroph proliferation. Exposure of cultured male rat pituitary cells to IGF-I (10(-7) M) or VIP (10(-7) M) stimulated the MAPK cascade. Studies in GH4C1 cells, with an expression vector for Rap1 GTPase-activating protein (Rap1 GAP1), demonstrated reduced VIP-induced MAPK activation, indicating that VIP-dependent activation of the extracellular signal-regulated kinase (ERK) pathway requires PKA-Rap1 signaling. IGF-I induced cAMP-response element (CRE)-binding protein (CREB) phosphorylation through the Ras-MAPK pathway, whereas VIP phosphorylated CREB directly via PKA. The mechanisms that regulate IGF-I-and VIP-CREB-dependent gene transcription were examined using GH4C1 cells transiently transfected with a CRE reporter gene. IGF-I and VIP stimulation of CRE-mediated transcription required activation of both Ras-MAPK and cAMP/PKA signaling. This activation was blocked in the presence of Rap1 GAP1. In summary, we showed that IGF-I and VIP stimulated MAPK activity and the phosphorylation of CREB in pituitary cells. Furthermore, VIP-dependent activation of PKA-Rap1-ERK pathways mediated VIP and IGF-I effects on CREB-dependent transcription in GH4C1 cells. Thus, it is possible that VIP- and IGF-I-induced lactotroph proliferation may involve Rap1.
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