Tyrosine phosphorylation and activation of Bruton tyrosine kinase upon Fc epsilon RI cross-linking.
Tyrosine phosphorylation of several cellular proteins is one of the earliest signaling events induced by cross-linking of the high-affinity receptor for immunoglobulin E (Fc epsilon RI) on mast cells or basophils. Tyrosine kinases activated during this process include the Src family kinases, Lyn, c-Yes, and c-Src, and members of another subfamily, Syk and PTK72 (identical or highly related to Syk). Recently, some of us described two novel tyrosine kinases, Emb and Emt, whose expression was limited to subsets of hematopoietic cells, including mast cells. Emb turned out to be identical to Btk, a gene product defective in human X-linked agammaglobulinemia and in X-linked immunodeficient (xid) mice. Here we report that Fc epsilon RI cross-linking induced rapid phosphorylation on tyrosine, serine, and threonine residues and activation of Btk in mouse bone marrow-derived mast cells. A small fraction of Btk translocated from the cytosol to the membrane compartment following receptor cross-linking. Tyrosine phosphorylation of Btk was not induced by either a Ca2+ ionophore (A23187), phorbol 12-myristate 13-acetate, or a combination of the two reagents. Co-immunoprecipitation between Btk and receptor subunit beta or gamma was not detected. The data collectively suggest that Btk is not associated with Fc epsilon but that its activation takes place prior to protein kinase C activation and plays a novel role in the Fc epsilon RI signaling pathway.
Kawakami
Y
Y
Division of Immunobiology, La Jolla Institute for Allergy and Immunology, California 92037.
Yao
L
L
Miura
T
T
Tsukada
S
S
Witte
O N
ON
Kawakami
T
T
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D002451:Cell Compartmentation; D004789:Enzyme Activation; D066298:In Vitro Techniques; D008407:Mast Cells / Q000201:enzymology; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011940:Receptor Aggregation; D017455:Receptors, IgE / Q000378:metabolism*; D015398:Signal Transduction; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism; D019061:src-Family Kinases
D008934:Mitogens; D017455:Receptors, IgE; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; C000625951:Btk protein, mouse; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases