Recently, we have reported that the CacyBP/SIP protein binds ERK1/2 (Kilanczyk et al., BBRC, 2009). In this work we show that CacyBP/SIP exhibits a phosphatase activity toward ERK1/2 kinases while its E217K mutant does not. The K(m) and V(max) values established for a standard phosphatase substrate, p-NPP, are 16.9±3.6 mM and 4.3±0.4 μmol/min, respectively. The CacyBP/SIP phosphatase activity is decreased by okadaic acid (IC(50)=45 nM). Our experimental results are supported by a theoretical analysis which revealed important sequence similarities between CacyBP/SIP and the phosphatase-like proteins as well as certain MAP kinase phosphatases.
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