Previous works revealed the presence of a Ca(2+)-dependent protein kinase (p60) and a Ca(2+)-independent protein kinase (p105) in the mantle tissue from the sea mussel Mytilus galloprovincialis Lmk. The expression of both isoforms shows a balance between cytosolic and membrane fractions in mantle, gills, and hepatopancreas, whereas, in hemocytes, their expression is mainly cytosolic, as happens in muscle tissues with p60 alone. Both enzymatic forms contain phosphorylated serines, and no phosphorylation was detected in tyrosines. Only the form p105 mediates the PMA-induced activation of the hemocytes of M. galloprovincialis, and it does so by a process of down-regulation. The form p60 does not respond to the presence of the phorbol ester, suggesting structural differences related to the binding sites of the diacylglycerol.