title: Biochemical and cellular implications of a dual lipase-GEF function of phospholipase D2 (PLD2).
abstract: PLD2 plays a key role in cell membrane lipid reorganization and as a key cell signaling protein in leukocyte chemotaxis and phagocytosis. Adding to the large role for a lipase in cellular functions, recently, our lab has identified a PLD2-Rac2 binding through two CRIB domains in PLD2 and has defined PLD2 as having a new function, that of a GEF for Rac2. PLD2 joins other major GEFs, such as P-Rex1 and Vav, which operate mainly in leukocytes. We explain the biochemical and cellular implications of a lipase-GEF duality. Under normal conditions, GEFs are not constitutively active; instead, their activation is highly regulated. Activation of PLD2 leads to its localization at the plasma membrane, where it can access its substrate GTPases. We propose that PLD2 can act as a "scaffold" protein to increase efficiency of signaling and compartmentalization at a phagocytic cup or the leading edge of a leukocyte lamellipodium. This new concept will help our understanding of leukocyte crucial functions, such as cell migration and adhesion, and how their deregulation impacts chronic inflammation.
authors: Wright State University School of Medicine, Department of Biochemistry and Molecular Biology, Dayton, OH, USA. julian.cambronero@wright.edu
authors: Julian
authors: J
authors: Gomez-Cambronero
mesh_terms: D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008049:Lipase / Q000378:metabolism*; D010739:Phospholipase D / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D008049:Lipase; C105606:phospholipase D2; D010739:Phospholipase D