Functional interaction of caveolin-1 with Bruton's tyrosine kinase and Bmx.
Bruton's tyrosine kinase (Btk), a member of the Tec family of protein-tyrosine kinases, has been shown to be crucial for B cell development, differentiation, and signaling. Mutations in the Btk gene lead to X-linked agammaglobulinemia in humans and X-linked immunodeficiency in mice. Using a co-transfection approach, we present evidence here that Btk interacts physically with caveolin-1, a 22-kDa integral membrane protein, which is the principal structural and regulatory component of caveolae membranes. In addition, we found that native Bmx, another member of the Tec family kinases, is associated with endogenous caveolin-1 in primary human umbilical vein endothelial cells. Second, in transient transfection assays, expression of caveolin-1 leads to a substantial reduction in the in vivo tyrosine phosphorylation of both Btk and its constitutively active form, E41K. Furthermore, a caveolin-1 scaffolding peptide (amino acids 82--101) functionally suppressed the autokinase activity of purified recombinant Btk protein. Third, we demonstrate that mouse splenic B-lymphocytes express substantial amounts of caveolin-1. Interestingly, caveolin-1 was found to be constitutively phosphorylated on tyrosine 14 in these cells. The expression of caveolin-1 in B-lymphocytes and its interaction with Btk may have implications not only for B cell activation and signaling, but also for antigen presentation.
Vargas
Leonardo
L
Clinical Research Center, Karolinska Institute, Huddinge University Hospital, SE-141 86 Huddinge, Sweden.
Nore
Beston F
BF
Berglof
Anna
A
Heinonen
Juhana E
JE
Mattsson
Pekka T
PT
Smith
C I Edvard
CI
Mohamed
Abdalla J
AJ
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology; D001665:Binding Sites; D051242:Caveolin 1; D022461:Caveolins / Q000032:analysis / Q000502:physiology*; D005677:G(M1) Ganglioside / Q000032:analysis; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism
D051242:Caveolin 1; D022461:Caveolins; D005677:G(M1) Ganglioside; D014443:Tyrosine; C492367:BMX protein, human; C492366:Bmx protein, mouse; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; C000625951:Btk protein, mouse