Nontranscriptional regulation of SYK by the coactivator OCA-B is required at multiple stages of B cell development.
OCA-B was originally identified as a nuclear transcriptional coactivator that is essential for antigen-driven immune responses. The later identification of a membrane bound, myristoylated form of OCA-B suggested additional, unique functions in B cell signaling pathways. This study has shown that OCA-B also functions in the pre-B1-to-pre-B2 cell transition and, most surprisingly, that it directly interacts with SYK, a tyrosine kinase critical for pre-BCR and BCR signaling. This unprecedented type of interaction-a transcriptional coactivator with a signaling kinase-occurs in the cytoplasm and directly regulates SYK stability. This study indicates that OCA-B is required for pre-BCR and BCR signaling at multiple stages of B cell development through its nontranscriptional regulation of SYK. Combined with the deregulation of OCA-B target genes, this may help explain the multitude of defects observed in B cell development and immune responses of Oca-b-/- mice.
Siegel
Rachael
R
Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Kim
Unkyu
U
Patke
Alina
A
Yu
Xin
X
Ren
Xiaodi
X
Tarakhovsky
Alexander
A
Roeder
Robert G
RG
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology*; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D002478:Cells, Cultured; D004795:Enzyme Stability; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D007075:Immunoglobulin M / Q000378:metabolism; D007150:Immunohistochemistry; D015851:Interleukin-7 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D000072377:Syk Kinase; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic
D007075:Immunoglobulin M; D015851:Interleukin-7; D047908:Intracellular Signaling Peptides and Proteins; C490424:Pou2af1 protein, mouse; D011956:Receptors, Cell Surface; D015534:Trans-Activators; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse