PROTEIN-KINASE ACTIVITY OF SIGA ANTIBODIES FROM HUMAN-MILK - CATALYTICALLY ACTIVE ANTIBODIES IN NORMAL HUMANS

A fraction of class A secreted immunoglobulins (sIgA) from the milk of healthy mothers was sequentially purified by chromatography on protein A Sepharose (in the presence of 18 Triton X-100), Toyopear 1 HW-55, Sepharose 4B (to remove anti-polysaccharide antibodies), DEAE-cellulose (to separate IgG and sIgA antibodies), and on affinity sorbent with immobilized ATP and casein. The material obtained exhibited the properties of sIgA antibodies and was free of protein impurities. Secreted immunoglobulins A were able to phosphorylate casein (but not histones) at serine residues in presence of gamma-[P-32]ATP. This activity was resistant to acidic shock (pH = 2.3), bound tightly with immobilized antibodies against the H chain of IgA, and was eluted in the same peak with antibodies. The sIgA-ATP complex was stable during gel filtration. Affinity modification of sIgA with ATP analogs (up to 2-3 moles per mole protein) resulted in labeling of light chains. Under dissociating conditions only light chains were sorbed on ATP-Sepharose. Optimal conditions for sIgA kinase activity substantially differed from those described for protein kinases. It was concluded that kinase activity is the first example of catalytic function of sIgA, and that normal humans may have natural abzymes which catalyze synthesis rather than hydrolysis.