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.
Akt, also known as protein kinase B (PKB), is a serine ⁄ threonine protein kinase that plays a pivotal role in many physiological processes, including metabolism, development, cell cycle progression, migration and survival [1][2][3][4]. The Akt subfamily of protein kinases consists of three isoforms -Akt1, Akt2 and Akt3 (also termed PKBa, PKBb and PKBc) -which are the products of distinct genes. All three proteins share a conserved tertiary structure of an N-terminal pleckstrin homology domain, a kinase domain and a C-terminal regulatory domain containing the hydrophobic motif phosphorylation site [5]. While the homology between the three isoforms allows for a degree of functional redundancy [1], there also seems to be considerable scope for isoform-specific activation and substrate specificity [3,6].Akt plays an integral role in the phosphoinositide 3-kinase (PI3K) signaling pathways. PI3K pathways are activated in response to extracellular signals mediated by cell-surface receptors of the G protein-coupled receptor (GPCR), integrin and growth factor ⁄ receptor tyrosine kinase (RTK) superfamilies. Receptor-mediated activation of PI3K results in the generation of phosphatidylinositol (3,4,5)-trisphosphate from phosphatidylinositol (4,5)-bisphosphate, a reaction that is reversed by the enzymes phosphatase and tensin homologue (PTEN) and SH2-domain-containing inositol polyphosphate 5-phosphatase (SHIP). Both Akt and
The dinoflagellates have very large genomes encoded in permanently condensed and histoneless chromosomes. Sequence alignment identified significant similarity between the dinoflagellate chromosomal histonelike proteins of Crypthecodinium cohnii (HCCs) and the bacterial DNA-binding and the eukaryotic histone H1 proteins. Phylogenetic analysis also supports the origin of the HCCs from histone-like proteins of bacteria.
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