Activation of BTK by a phosphorylation mechanism initiated by SRC family kinases.
Bruton's tyrosine kinase (BTK) is pivotal in B cell activation and development through its participation in the signaling pathways of multiple hematopoietic receptors. The mechanisms controlling BTK activation were studied here by examination of the biochemical consequences of an interaction between BTK and SRC family kinases. This interaction of BTK with SRC kinases transphosphorylated BTK on tyrosine at residue 551, which led to BTK activation. BTK then autophosphorylated at a second site. The same two sites were phosphorylated upon B cell antigen receptor cross-linking. The activated BTK was predominantly membrane-associated, which suggests that BTK integrates distinct receptor signals resulting in SRC kinase activation and BTK membrane targeting.
Rawlings
D J
DJ
Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90095-1662, USA.
Scharenberg
A M
AM
Park
H
H
Wahl
M I
MI
Lin
S
S
Kato
R M
RM
Fluckiger
A C
AC
Witte
O N
ON
Kinet
J P
JP
D016475:3T3 Cells; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology*; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000201:enzymology; D004789:Enzyme Activation; D007075:Immunoglobulin M / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D009154:Mutation; D010748:Phosphopeptides / Q000032:analysis; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism*
D007075:Immunoglobulin M; D010748:Phosphopeptides; D011947:Receptors, Antigen, B-Cell; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625951:Btk protein, mouse; D019061:src-Family Kinases