Interconnected ganglia

Victor Tybulewicz group project:

Syk

Syk is a protein tyrosine kinase activated by BCR stimulation (Turner et al, 2000). Several years ago we made mice deficient in Syk and showed that the mutation causes a complete block in B cell development. This block is due to defects at two stages. Firstly there is a partial block at the pre-BCR signalling checkpoint, and then a complete block between the immature B cell and mature recirculating B cell compartment (Turner et al, 1995; Turner et al, 1997). More recently we have discovered that the partial block at the pre-BCR checkpoint is due to redundancy between Syk and a related tyrosine kinase, ZAP-70. Mice mutant in both Syk and ZAP-70 show a complete block at the pre-BCR checkpoint as well as a failure of heavy chain allelic exclusion (Schweighoffer et al, 2003). Current work is focused on using a conditional allele of Syk to study Syk function in mature B cells.

Schematic structure of Syk/ZAP-70 family protein tyrosine kinases

Schematic structure of Syk/ZAP-70 family protein tyrosine kinases

Schematic structure oThe tandem SH2 domains and the kinase domain are shown as orange and green cylinders respectively. Purple tubes represent the linker region connecting the SH2 and kinase domains. In comparison with the alternatively spliced isoform Syk-B, Syk contains an insert of 23 amino acids (dark purple) within the linker region. Tyrosine residues (Y) in Syk which have been shown to undergo phosphorylation are indicated – these may be important in regulating enzymatic activity or recruiting other signaling proteins (Turner et al., 2000).

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