Regulation of phospholipase C gamma isoforms in haematopoietic cells: why one, not the other?
Phospholipase C gamma (PLCgamma) isoforms are critical for the generation of calcium signals in haematopoietic systems in response to the stimulation of immune receptors. PLCgamma is unique amongst phospholipases in that it is tightly regulated by the action of a number of tyrosine kinases. It is itself directly phosphorylated on a number of tyrosines and contains several domains through which it can interact with other signalling proteins and lipid products such as phosphatidylinositol 3,4,5-trisphosphate. Through this network of interactions, PLCgamma is activated and recruited to its substrate, phosphatidylinositol 4,5-bisphosphate, at the membrane. Both isoforms of PLCgamma, PLCgamma1 and PLCgamma2, are present in haematopoietic cells. The signalling cascade involved in the regulation of these two isoforms varies between cells, though the systems are similar for both PLCgamma1 and PLCgamma2. We will compare these cascades for both PLCgamma1 and PLCgamma2 and discuss possible reasons as to why one form of PLCgamma and not the other is required for signalling in specific haematopoietic cells, including T lymphocytes, B lymphocytes, platelets, and mast cells.
Wilde
J I
JI
Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK. jonathan.wilde@pharm.ox.ac.uk
Watson
S P
SP
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001773:Blood Cells / Q000502:physiology*; D001792:Blood Platelets / Q000502:physiology; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism*; D046911:Macromolecular Substances; D051379:Mice; D008954:Models, Biological; D051966:Phospholipase C gamma; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology; D010738:Type C Phospholipases / Q000737:chemistry / Q000378:metabolism*
D007527:Isoenzymes; D046911:Macromolecular Substances; D020033:Protein Isoforms; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma