Cytoplasmic Signaling


Cytoplasmic signaling proteins play crucial roles in cell cycle, targeted proteolysis, protein trafficking, cytoskeletal organization, and gene expression. Mutations in or misregulation of these proteins cause, or are correlated with, various diseases including cancer, diabetes and rheumatoid arthritis. Cytoplasmic signaling, especially in the lipid signaling and G-protein signaling pathways, is dominated by protein phosphorylation by kinases, which represent one of the most common targets of therapeutics, targeted in about 25% of drug discovery programs worldwide.

Cytoplasmic signaling is also transduced via secondary messengers, either small molecules produced by rapid synthesis through enzyme activation or ions (like calcium) introduced through transmembrane channels. Secondary messengers diffuse within the cell and communicate through G-proteins, ion channels, and a variety of other proteins, propagating the signaling cascade.

Lipid Signaling

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Bioactive lipids, generated during the remodeling of membrane lipids by activated lipases, serve as intra- and extracellular mediators in cell signaling.
Calcium Signaling

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The divalent cation calcium (Ca2+) is used by cells as a second messenger to control many cellular processes including muscle contraction, secretion, metabolism, neuronal excitability, cell proliferation, and cell death.
G-protein Signaling

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G proteins are heterotrimeric GTP-binding signaling proteins and are composed of α, β and γ subunits encoded by distinct genes. Bound to the intracellular face of G-protein coupled receptors (GPCRs), G-proteins mediate cytoplasmic transduction of extracellular stimuli.
Small GTPase Signaling

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Small GTPases are 20-30 kDa enzymes that catalyze the hydrolysis of GTP to GDP and are a subset of G proteins. Two important subfamilies of small GTPases are the Ras and Rho families, which are particularly important for cytoskeletal signaling.