The ubiquitously expressed Csk adaptor protein Cbp is dispensable for embryogenesis and T-cell development and function.
Regulation of Src family kinase (SFK) activity is indispensable for a functional immune system and embryogenesis. The activity of SFKs is inhibited by the presence of the carboxy-terminal Src kinase (Csk) at the cell membrane. Thus, recruitment of cytosolic Csk to the membrane-associated SFKs is crucial for its regulatory function. Previous studies utilizing in vitro and transgenic models suggested that the Csk-binding protein (Cbp), also known as phosphoprotein associated with glycosphingolipid microdomains (PAG), is the membrane adaptor for Csk. However, loss-of-function genetic evidence to support this notion was lacking. Herein, we demonstrate that the targeted disruption of the cbp gene in mice has no effect on embryogenesis, thymic development, or T-cell functions in vivo. Moreover, recruitment of Csk to the specialized membrane compartment of "lipid rafts" is not impaired by Cbp deficiency. Our results indicate that Cbp is dispensable for the recruitment of Csk to the membrane and that another Csk adaptor, yet to be discovered, compensates for the loss of Cbp.
Dobenecker
Marc-Werner
MW
Laboratory of Lymphocyte Signaling, The Rockefeller University, 1230 York Avenue, Box 301, New York, NY 10021, USA. dobenem@mail.rockefeller.edu
Schmedt
Christian
C
Okada
Masato
M
Tarakhovsky
Alexander
A
D034001:Adaptor Protein Complex Subunits / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000941:Antigens / Q000378:metabolism; D000081247:CSK Tyrosine-Protein Kinase; D002454:Cell Differentiation; D017635:Clonal Anergy; D047108:Embryonic Development; D018507:Gene Expression Regulation, Developmental; D021962:Membrane Microdomains / Q000378:metabolism; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D019061:src-Family Kinases
D034001:Adaptor Protein Complex Subunits; D000941:Antigens; D008565:Membrane Proteins; C498709:Pag1 protein, mouse; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases