Clustered syk tyrosine kinase domains trigger phagocytosis.
Phagocytosis is a phylogenetically primitive mechanism adapted by specialized cells of the immune system to ingest particulate pathogens. Recent evidence suggests that the program of specific cytoskeletal rearrangements that underlies phagocytosis may share elements with the antigen receptor signaling pathway in lymphocytes. Tyrosine phosphorylation, necessary for both lymphocyte effector function and phagocytosis, is thought to allow cytoskeletal elements to couple to the intracellular domains of antigen and Fc receptor subunits. We show here that the intracellular domains of the receptors are not inherently required for cytoskeletal coupling. Chimeric transmembrane proteins bearing syk but not src family tyrosine kinase domains are capable of autonomously triggering phagocytosis and redistribution of filamentous actin in COS cells. These responses cannot be initiated by a receptor chimera bearing a point mutation in the syk catalytic domain, and the kinase domain alone is sufficient for initiating cytoskeletal coupling.
Greenberg
S
S
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Chang
P
P
Wang
D C
DC
Xavier
R
R
Seed
B
B
D000199:Actins / Q000032:analysis; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002522:Chlorocebus aethiops; D003599:Cytoskeleton / Q000502:physiology; D004792:Enzyme Precursors / Q000096:biosynthesis / Q000378:metabolism*; D004912:Erythrocytes / Q000502:physiology*; D006801:Humans; D007074:Immunoglobulin G; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D008565:Membrane Proteins / Q000096:biosynthesis / Q000378:metabolism; D010587:Phagocytosis; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000378:metabolism*; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism; D012756:Sheep; D015398:Signal Transduction; D000072377:Syk Kinase; D014162:Transfection
D000199:Actins; D004792:Enzyme Precursors; D007074:Immunoglobulin G; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D002118:Calcium