Molecular mechanisms mediating the G protein-coupled receptor regulation of cell cycle progression

Abstract

G protein-coupled receptors are key regulators of cellular communication, mediating the efficient coordination of a cell's responses to extracellular stimuli. When stimulated these receptors modulate the activity of a wide range of intracellular signalling pathways that facilitate the ordered development, growth and reproduction of the organism. There is now a growing body of evidence examining the mechanisms by which G protein-coupled receptors are able to regulate the expression, activity, localization and stability of cell cycle regulatory proteins that either promote or inhibit the initiation of DNA synthesis. In this review, we will detail the intracellular pathways that mediate the G protein-coupled receptor regulation of cellular proliferation, specifically the progression from the G1 phase to the S phase of the cell cycle.

Luteinizing Hormone–Induced Up-Regulation of ErbB-2 Is Insufficient Stimulant of Growth and Invasion in Ovarian Cancer Cells

“…Based on this reasoning, an EGFR kinase and an ErbB-2 kinase inhibitor were tested and both inhibitors blocked the LH-induced up-regulation of ErbB-2. LH is also known to cause the release of heparin-bound EGF by activating MMPs at the cell surface (3,58). In our system, however, the broad-spectrum MMP inhibitor was ineffective at blocking LH-induced ErbB-2 upregulation, suggesting that the activation of protease activities is not involved in the LH-induced up-regulation of ErbB-2.…”

“…Intracellular phosphorylation cascades activated by G protein -coupled receptors constitute one cellular mechanism for responding to external stimuli and regulating physiologic events (58). To define some of the intracellular phosphorylation pathways involved in LH-induced ErbB-2 up-regulation, the ability of specific kinase inhibitors to block the LH-induced ErbB-2 up-regulation was investigated.…”

G Protein-Coupled Receptors-Induced Activation of Extracellular Signal-Regulated Protein Kinase (ERK) and Sodium-Proton Exchanger Type 1 (NHE1)

“…Although the mechanisms by which GPCRs control the activity of ERK vary between receptor and cell type, typically there are three categories of mechanisms: (1) signals that initiate classical G protein effectors, e.g., protein kinase A or protein kinase C causing the production of second messengers, (2) mechanisms that involve cross-talk between GPCRs and classical receptor tyrosine kinases, e.g., "transactivation" of epidermal growth factor (EGF) receptors, and (3) signals initiated by direct interaction between beta-arrestins and components of the MAP kinase cascade, e.g., beta-arrestin "scaffolds". Mitogenic pathways activated by different G families including activation of adenylyl cyclase/cAMP and phospholipase C /protein kinase C second messenger pathways have been described in detail (reviewed by New & Wong, 2007). Angiotensin II promotes DNA synthesis and proliferation in many cell types by activating the G q -coupled AT 1 receptor.…”

“…The intracellular pathways that mediate GPCR -induced ERK activation and regulation of cellular proliferation were recently reviewed by New & Wong (New & Wong, 2007).…”

Examination of the relevance of PI3K and PTEN pathway in Ustilago maydis.

“…Also, the G-alpha subunit activates Srcdependent integrin signaling which can activate PI3K. (New and Wong, 2007).…”