Nerve growth factor. A structural relationship between its proteolytic and leukocyte-chemotactic active sites

Summary High molecular weight mouse nerve growth factor(H M W-NGF), in addition to its effects on certain neural elements, is also chemotactic for human polymorphonuclear leukocytes. One of the subunits of H M W-NGF is a protease of the serine family and its active site contains a serine residue and a closely-neighboring histidine residue that are both essential for proteolysis. Elimination of enzyme activity by irreversibly blocking the single serine has no effect on leukotaxis, but blocking the histidine abolishes leukotaxis. These results suggest the possibility that part of the proteolytic active site of this enzyme may have evolved to perform more than one, completely different, biologic function — proteolysis as well as nonproteolytically mediated chemotaxis.Abbreviations HMW-NGF mouse submandibular gland nerve growth factor, purified as in Ref. 1 - DFP diisopropyl-phosphofluoridate - DIP-NGF diisopropyl-phosphoryl-NGF; phe-pro-arg-CH₂C1, D-phenylalanyl-L-propyl-L-argininyl chloromethyl ketone; TLCK, N-p-tosyl-L-lysine chloromethyl ketone - TAME N-p-tosyl L-arginine methyl ester - EDTA ethylenediamine tetraacetic acid