Linked Life Data

16585544

Source:http://linkedlifedata.com/resource/pubmed/id/16585544

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2006-4-4
pubmed:abstractText
Bruton's tyrosine kinase (Btk) and the adapter protein SLP-65 (Src homology 2 domain-containing leukocyte-specific phosphoprotein of 65 kDa) transmit precursor BCR (pre-BCR) signals that are essential for efficient developmental progression of large cycling into small resting pre-B cells. We show that Btk- and SLP-65-deficient pre-B cells have a specific defect in Ig lambda L chain germline transcription. In Btk/SLP-65 double-deficient pre-B cells, both kappa and lambda germline transcripts are severely reduced. Although these observations point to an important role for Btk and SLP-65 in the initiation of L chain gene rearrangement, the possibility remained that these signaling molecules are only required for termination of pre-B cell proliferation or for pre-B cell survival, whereby differentiation and L chain rearrangement is subsequently initiated in a Btk/SLP-65-independent fashion. Because transgenic expression of the antiapoptotic protein Bcl-2 did not rescue the developmental arrest of Btk/SLP-65 double-deficient pre-B cells, we conclude that defective L chain opening in Btk/SLP-65-deficient small resting pre-B cells is not due to their reduced survival. Next, we analyzed transgenic mice expressing the constitutively active Btk mutant E41K. The expression of E41K-Btk in Ig H chain-negative pro-B cells induced 1) surface marker changes that signify cellular differentiation, including down-regulation of surrogate L chain and up-regulation of CD2, CD25, and MHC class II; and 2) premature rearrangement and expression of kappa and lambda light chains. These findings demonstrate that Btk and SLP-65 transmit signals that induce cellular maturation and Ig L chain rearrangement independently of their role in termination of pre-B cell expansion.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
176
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4543-52
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed-meshheading:16585544-Adaptor Proteins, Signal Transducing, pubmed-meshheading:16585544-Animals, pubmed-meshheading:16585544-B-Lymphocytes, pubmed-meshheading:16585544-Base Sequence, pubmed-meshheading:16585544-Carrier Proteins, pubmed-meshheading:16585544-Cell Differentiation, pubmed-meshheading:16585544-Cell Proliferation, pubmed-meshheading:16585544-Cell Survival, pubmed-meshheading:16585544-DNA, Complementary, pubmed-meshheading:16585544-Gene Rearrangement, B-Lymphocyte, Light Chain, pubmed-meshheading:16585544-Interleukin-7, pubmed-meshheading:16585544-Mice, pubmed-meshheading:16585544-Mice, Inbred C57BL, pubmed-meshheading:16585544-Mice, Knockout, pubmed-meshheading:16585544-Mice, Transgenic, pubmed-meshheading:16585544-Phosphoproteins, pubmed-meshheading:16585544-Protein-Tyrosine Kinases, pubmed-meshheading:16585544-Signal Transduction, pubmed-meshheading:16585544-Transcription, Genetic
pubmed:year
2006
pubmed:articleTitle
Bruton's tyrosine kinase and SLP-65 regulate pre-B cell differentiation and the induction of Ig light chain gene rearrangement.
pubmed:affiliation
Department of Immunology, Erasmus Medical Center, Rotterdam, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't