Jak3 is associated with CD40 and is critical for CD40 induction of gene expression in B cells.
CD40 is a receptor that is critical for the survival, growth, differentiation, and isotype switching of B lymphocytes. Although CD40 lacks intrinsic tyrosine kinase activity, its ligation induces protein tyrosine phosphorylation, which is necessary for several CD40-mediated events. We show that engagement of CD40 induces tyrosine phosphorylation and activation of Jak3 as well as of STAT3. Jak3 is constitutively associated with CD40, and this interaction requires a proline-rich sequence in the membrane-proximal region of CD40. Deletion of this sequence abolishes the capacity of CD40 to induce expression of CD23, ICAM-1, and lymphotoxin-alpha genes in B cells. These results indicate that signaling through Jak3 is activated by CD40 and plays an important role in CD40-mediated functions.
Hanissian
S H
SH
Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Geha
R S
RS
D001402:B-Lymphocytes / Q000201:enzymology* / Q000378:metabolism*; D002051:Burkitt Lymphoma; D019013:CD40 Antigens / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D006801:Humans; D050856:Interferon Regulatory Factor-1; D053616:Janus Kinase 3; D008024:Ligands; D014066:Palatine Tonsil / Q000166:cytology; D010449:Peptide Mapping; D010750:Phosphoproteins / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D014407:Tumor Cells, Cultured
D019013:CD40 Antigens; D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D008024:Ligands; D010750:Phosphoproteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3