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Characterization of SaBR, a novel murine cell surface protein

University of British Columbia

Regulation of hematopoiesis is a complex process consisting of multiple interactions involving cell surface proteins and soluble mediators. SaBR is a novel murine cell surface protein that is differentially expressed within the hematopoietic system in terms of cell lineage, location, developmental stage and activation status and as such is a candidate for a hematopoietic regulator. In the lymphocyte lineage, SaBR is expressed throughout B cell development, but is only found on mature single positive T cells. In vitro activation of purified splenic lymphocytes results in changes in SaBR expression dependent on the activator being used. In B cells, SaBR is downregulated following cross-linking of the B cell receptor in conjunction with a costimulatory stimulus, but is upregulated if two costimulatory signals are used. In T cells, SaBR upregulation is observed upon activation with phorbol ester plus ionophore and phorbol ester plus α-CD3. In addition, B220+SaBR+ sorted B cells were found to have a significantly higher tritiated thymidine incorporation than their negative counterparts in both non-activated and activated populations. Sequencing analysis of a cDNA encoding murine SaBR revealed an 820 a.a type I transmembrane protein with three putative extracellular domains. The amino terminal portion of SaBR encodes a somatomedin B-like domain and the other two extracellular domains have sequence similarity to a region of von Willibrand factor and the membrane proximal domains of the selectin and complement receptor families. A human cDNA was found to have 73% nucleotide identity to mouse SaBR and Northern analysis revealed the presence of two differentially expressed human SaBR mRNA products as compared to one for the mouse. When histochemical analysis was performed, unique SaBR expression patterns were detected in the kidney and stomach, suggesting a potential role for SaBR in these tissues. The studies described in this thesis indicate that SaBR is a unique transmembrane protein expressed in the hematopoietic system and may play a role in lymphocyte activation. At present, there is not enough data to make conclusions regarding SaBR function in the mouse; however, a model presenting SaBR as a regulator of lymphocyte activation is proposed.

Thesis/Dissertation

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2009-06-02

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http://hdl.handle.net/2429/8639

Medical Genetics

University of British Columbia

UBCV

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