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Structural Insights into Phospholipase Cɛ Function
Author(s) -
Rugema Ngango Yvon,
Prahalad Keshav,
Pearson Sean Patrick,
O'Neill Hannah,
Mbongo William,
GarlandKuntz Elisabeth,
Sieng Monita,
Lyon Angeline M
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.lb205
Subject(s) - guanine nucleotide exchange factor , phospholipase c , g protein coupled receptor , gtpase , g protein , microbiology and biotechnology , phosphatidylinositol , phospholipase , small gtpase , receptor , biology , phosphoinositide phospholipase c , gtpase activating protein , biochemistry , gq alpha subunit , signal transduction , chemistry , enzyme
Phospholipase Cɛ (PLCɛ) is a member of the PLC family of enzymes that hydrolyze phosphatidylinositol lipids downstream of G protein coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs). PLCɛ is unique among the PLC superfamily as it contains an N‐terminal CDC25 domain, which has guanine nucleotide exchange factor (GEF) activity towards small G proteins Rap1A, and two C‐terminal Ras association (RA) domains. The best characterized pathway leading to PLCɛ activation is mediated through β‐adrenergic receptor (βARs) signaling. Stimulation of these receptors culminates in the activation of the small GTPase, Rap1A, which binds directly to PLCɛ and translocates the complex to the Golgi. There, PLCɛ hydrolyzes phosphatidylinol‐4‐phosphate (PI4P). Prolonged activation of this pathway results in increased expression of hypertrophy‐related genes. However, how the structural basis of PLCɛ activity under basal conditions and upon activation by Rap1A are unknown. Towards this end, we have obtained the first high‐resolution insights into a catalytically active PLCɛ variant. These studies, together with biochemical analysis of the intramolecular contacts observed in the structure, provide the first molecular insights into this enzyme. Support or Funding Information This research is supported by American Heart Association Scientist Development Grant 16SDG29920017 and NIH 1R01HL141076‐01 to A.M.L This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .