![]() ![]() On the other hand, PKC provides negative feedback when it phosphorylates and inhibits both growth factor receptors and PI-PLCγ 1. PKC activates PLD and PLA 2 and provides positive feedback, because those enzymes produce more DAG to sustain the activation of PKC. PKCs can provide either positive or negative feedback to the signaling pathways that turn them on. ![]() The C2 regions target PKC isozymes to the plasma membrane, cytoskeleton, or nucleus. PKC isozymes are selective toward certain protein substrates. 46.12) producing constitutively active PKC isoforms.Īctivated PKCs have many potential targets in cells and are implicated in the regulation of cellular activities ranging from gene expression to cell motility to the generation of lipid second messengers. During apoptosis, caspases cleave off this regulatory domain (see Fig. Ca 2+-dependent PKC isozymes have C2 regions that mediate binding to phospholipids in the presence of Ca 2+. Phorbol esters, pharmacological activators of PKC that promote tumor formation in laboratory experiments, bind PKC in a fashion similar to DAG. DAG binding depends on phosphoglycerides, such as phosphatidylserine. DAG and other lipid second messengers bind C1 regions adjacent to the pseudosubstrate. Pseudosubstrates have alanine at the phosphorylation site instead of the serine found in substrates. Lipid second messengers activate PKC by dissociating an intramolecular pseudosubstrate sequence from the active site. Sphingosine may inhibit some PKC isozymes. Some, but not all, PKC isozymes also require Ca 2+ for activation. These diverse PKC isozymes provide a selective response to various lipid second messengers. Many lipid second messengers, including DAG, PIP 3, arachidonic acid, phosphatidic acid, and lysophosphatidylcholine activate one or more of the 10 PKC isozymes expressed by vertebrate cells ( Fig. In Cell Biology (Third Edition), 2017 Protein Kinase C ![]()
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