Initial events in Fc epsilon RI signal transduction.
Our current model of the events that occur in the first few seconds after Fc epsilon RI cross-linking focuses primarily on the role of tyrosine phosphorylation and its ability to direct specific protein-protein interactions through SH2 domains. Contact of a mast cell bearing appropriately liganded Fc epsilon RI with multivalent antigen results in the approximation of receptors initially into chains. The proximity of receptors in these chains allows the phosphorylation of their ARAMs by the lyn tyrosine kinase. ARAM phosphorylation results in binding of syk specifically to cross-linked receptors and its probable subsequent phosphorylation and activation by lyn. Activated syk then phosphorylates and activates PLC gamma 1 and PLC gamma 2, resulting in their activation and translocation to the membrane. The presence of active PLC gamma 1 and PLC gamma 2 on the cell membrane results in hydrolysis of membrane phosphatidyl inositol and the production of 1,4,5 inositol triphosphate. Inositol 1,4,5 triphosphate diffuses to the sarcoplasmic reticulum and causes the release of sequestered calcium. This model represents a snapshot of the current body of knowledge about Fc epsilon RI-mediated signal transduction. Given the rapid pace of research in this field, it will likely be incorrect or incomplete in at least some respects by the time of publication. Ideally, the information presented here should provide a framework on which to build for those interested in learning more about Fc epsilon RI in particular and multisubunit antigen receptors in general.
Scharenberg
A M
AM
National Institute of Allergy and Infectious Diseases, Rockville, MD 20852.
Kinet
J P
JP
D000818:Animals; D002118:Calcium / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011946:Receptors, Antigen / Q000378:metabolism*; D017455:Receptors, IgE / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D010716:Phosphatidylinositols; D011946:Receptors, Antigen; D017455:Receptors, IgE; D011505:Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases; D002118:Calcium