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

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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.

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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, αN-p-tosyl-L-lysine chloromethyl ketone

TAME:

αN-p-tosyl L-arginine methyl ester

EDTA:

ethylenediamine tetraacetic acid

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, College of Medicine, 32610, Gainesville, Florida, USA

    Michael Younga & Kathy L. Mungera

  2. Department of Immunology and Medical Microbiology, College of Medicine, 32610, Gainesville, Florida, USA

    Adrian P. Gee & Michael D. P. Boyleb

  3. Department of Pediatrics, College of Medicine, 32610, Gainesville, Florida, USA

    Adrian P. Gee & Michael D. P. Boyleb

  4. Department of Comparative and Experimental Pathology, College of Veterinary Medicine, University of Florida, 32610, Gainesville, Florida, USA

    Michael J. P. Lawman

Authors
  1. Michael Younga
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  2. Adrian P. Gee
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  3. Michael D. P. Boyleb
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  4. Michael J. P. Lawman
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  5. Kathy L. Mungera
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Younga, M., Gee, A.P., Boyleb, M.D.P. et al. Nerve growth factor. A structural relationship between its proteolytic and leukocyte-chemotactic active sites. Mol Cell Biochem 66, 65–69 (1985). https://doi.org/10.1007/BF00231825

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