Bruton's tyrosine kinase controls a sustained calcium signal essential for B lineage development and function.
Genetic data support a role for Btk during the B lineage development transitions regulated by signaling through both the pre-B and the B cell antigen receptors. Dysregulated signaling at each of these transitions can result in failure of these cell populations to proliferate and subsequent cell death. Btk-dependent IP3 production is crucial for maintaining the sustained calcium signal in response to BCR engagement and is likely to regulate a subset of transcriptional events essential for B lineage growth or survival. Identification of these Btk-dependent signals will be important in understanding B cell activation, differentiation, and cell death. This information may lead to therapies specifically targeting these events in B cell autoimmunity or malignancy and provide a fuller understanding of the appropriate target populations and potential negative consequences of Btk gene therapy in XLA. Identification of Btk/Tec family kinases in an increasing number of vertebrate and invertebrate cell lineages suggests that the link between Btk and the PLC gamma/IP3/calcium signaling pathways may be broadly conserved.
Rawlings
D J
DJ
Department of Pediatrics, Jonsson Comprehensive Cancer Center, University of California, Los Angeles 90095-1752, USA.
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000201:enzymology / Q000235:genetics; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*; D020013:Calcium Signaling / Q000502:physiology*; D002454:Cell Differentiation; D004789:Enzyme Activation; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008954:Models, Biological; D009154:Mutation; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D015398:Signal Transduction; D014960:X Chromosome / Q000235:genetics; D019061:src-Family Kinases / Q000378:metabolism
D011947:Receptors, Antigen, B-Cell; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; D019061:src-Family Kinases