A catalytically inactive form of protein kinase C-associated kinase/receptor interacting protein 4, a protein kinase C beta-associated kinase that mediates NF-kappa B activation, interferes with early B cell development.
Protein kinase C-associated kinase (PKK)/receptor interacting protein 4 (RIP4) is a protein kinase C (PKC) beta-associated kinase that links PKC to NF-kappaB activation. The kinase domain of PKK is similar to that of RIP, RIP2, and RIP3. We show in this study that PKK is expressed early during lymphocyte development and can be detected in common lymphoid progenitor cells. Targeting of a catalytically inactive version of PKK to lymphoid cells resulted in a marked impairment in pro-B cell generation in the bone marrow. Although peripheral B cell numbers were markedly reduced, differentiation into follicular and marginal zone B cells was not defective in these mice. B-1a and B-1b B cells could not be detected in these mice, but this might be a reflection of the overall defect in B cell production observed in these animals. In keeping with a possible link to PKCbeta, peripheral B cells in these mice exhibit a defect in anti-IgM-mediated proliferation. These studies suggest that PKK may be required early in B cell development and for BCR-mediated B cell proliferation.
Cariappa
Annaiah
A
Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02129, USA.
Chen
Luojing
L
Haider
Khaleda
K
Tang
Mei
M
Nebelitskiy
Eugene
E
Moran
Stewart T
ST
Pillai
Shiv
S
D000818:Animals; D017089:Ankyrin Repeat / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology* / Q000201:enzymology* / Q000473:pathology; D001854:Bone Marrow Cells / Q000166:cytology / Q000201:enzymology; D002384:Catalysis; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D004789:Enzyme Activation / Q000235:genetics / Q000276:immunology; D006131:Growth Inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000201:enzymology; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D008213:Lymphocyte Activation / Q000235:genetics; D008231:Lymphopenia / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D064546:Protein Kinase C beta; D011494:Protein Kinases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D011947:Receptors, Antigen, B-Cell / Q000502:physiology
D006131:Growth Inhibitors; D007527:Isoenzymes; D016328:NF-kappa B; D011947:Receptors, Antigen, B-Cell; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C430884:Ripk4 protein, mouse; D011493:Protein Kinase C; D064546:Protein Kinase C beta