Structural insights into the regulation of PLC-β2 Public Deposited

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Alternate title
  • Structural insights into the regulation of PLC-[beta]2
Last Modified
  • March 21, 2019
Creator
  • Jezyk, Mark R.
    • Affiliation: School of Medicine, Department of Biochemistry and Biophysics
Abstract
  • The phospholipase C (PLC) family of enzymes mediates signal transduction events initiated at the cell surface by a myriad of receptors. When activated by signaling pathways initiated by cell surface receptors, PLC enzymes catalyze the hydrolysis of the minor membrane lipid, phosphatidyl inositol (4,5) bis-phosphate into the second messengers, diacylglycerol and inositol (1,4,5) tris-phosphate. These second messengers then stimulate the activity of protein kinase C and the release of intracellular calcium levels to regulate a vast array of cellular responses. The PLC family of enzymes is composed of six subfamilies all containing a conserved core architecture. This structural core is elaborated by various accessory domains, which facilitate the binding of activators and confer tight and specific regulation of PLC activity downstream of diverse signaling cascades. To gain an understanding of the molecular mechanisms of such regulation we have determined the structures of the conserved core of PLC-β2 in the absence and presence of its activator, the small GTPase, Rac1. These structures and the accompanying biochemical characterization reveal the overall organization of the enzyme and elucidate several mechanisms of its activation. The work presented here greatly expands the understanding of PLC regulation and builds the foundation for further work aimed at identifying the physiological role of PLC signaling cascades.
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  • In Copyright
Advisor
  • Sondek, John
Degree granting institution
  • University of North Carolina at Chapel Hill
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  • Open access
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