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Since IP3 generation and its binding to IP3 receptors are essential for the BCR induced calcium mobilization from intracellular pools (Sugawara et al., 1997; Takata et al., 1995), our data indicate that PIR B aborts the initial release of Ca2+ from the intracellular pools by inhibiting IP3 generation through down regulation of PLC 2. As SHP 1 and SHP 2 are required for PIR B mediated inhibition of calcium mobilization (Maeda et al., 1998), the simplest interpretation for inhibition of PLC 2 tyrosine phosphorylation is that PLC 2 serves as a direct substrate of SHP 1 and SHP 2. Assuming that PLC 2 is a sole substrate of SHP 1 and SHP 2 by PIR B, one would predict that engagement of PIR B with BCR dephosphorylates only PLC 2 rather than many substrates.
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