Protein kinase C-associated kinase is not required for the development of peripheral B lymphocyte populations.
Protein kinase C-associated kinase (PKK; DIK/RIP4) is an ankyrin-repeat containing serine/threonine receptor-interacting protein (RIP)-family kinase that can activate NFkappaB, and is required for keratinocyte development. In earlier studies, the expression of a catalytically inactive mutant of PKK in the B cell lineage resulted in a marked decrease in peripheral B cells in the spleen and a severe reduction of B-1 B cells. Here we explore the consequences of a null mutation in PKK with respect to the generation of peripheral B cell lineages and the activation of NFkappaB. We show that PKK is not required for the production of B cells in the bone marrow or for the development and maintenance of all mature B lymphocyte populations. We also show that PKK is not required for the activation of NFkappaB downstream of the BCR, CD40, or TLR-4 in B cells. Taken together, these data demonstrate that the loss of this RIP-family kinase does not compromise B lymphocyte development and maintenance, but leaves open the possibility that PKK may have a redundant role in these processes.
Moran
Stewart T
ST
Massachusetts General Hospital Cancer Center, Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA.
Cariappa
Annaiah
A
Liu
Haoyuan
H
Boboila
Cristian
C
Shi
Hai Ning
HN
Holland
Pamela M
PM
Peschon
Jacques J
JJ
Pillai
Shiv
S
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000201:enzymology*; D001853:Bone Marrow / Q000276:immunology; D019013:CD40 Antigens / Q000378:metabolism; D019070:Cell Lineage; D004789:Enzyme Activation; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D000097782:NF-kappaB-Inducing Kinase
D019013:CD40 Antigens; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011947:Receptors, Antigen, B-Cell; D051197:Toll-Like Receptor 4; D000097782:NF-kappaB-Inducing Kinase; C493487:Tlr4 protein, mouse; C430884:Ripk4 protein, mouse