Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One of the esteroproteinases present in the submandibular glands of female mice was purified and characterized. The enzyme, designated proteinase F in this report, had a pI value of 4.6 and a molecular weight of 27600, being comprised of two subunits of 10000 and 18000 daltons. The amino acid composition of proteinase F resembled that of the epidermal growth factor-binding protein, but antiserum against proteinase F only reacted weakly against the binding protein. Proteinase F had an optimum pH at around 9.0 and was strongly inhibited by Cu2+ and Hg2+ (42 and 76% inhibition, respectively, at a concentration of 4 x 10(-6) M). It was also inhibited by aprotinin, phenylmethylsulfonylfluoride, iodoacetamide, leupeptin, antipain, and benzamidine but neither by trypsin inhibitors from pancrease, soybean, or ovomucoid, nor by TLCK, TPCK, and epsilon-amino-n-caproic acid. Although its actual physiological function has yet to be determined, these properties indicate that proteinase F is a new enzyme, being distinguished from known proteinases, kallikrein, plasmin, trypsin, chymotrypsin, tonin, angiotensin-converting enzyme, proteinase A (beta-nerve growth factor endopeptidase), proteinase D (epidermal growth factor-binding protein), P-esterase, renin A, and renin C. Proteinase F was present in the submandibular glands of female mice more abundantly than in those of males, but it increased in males following castration. Thus, proteinase F appears to be affected by male hormones in vivo.
 ...
PMID:A new esteroproteinase (proteinase F) from the submandibular glands of female mice. 633 33

Monoamine-activated alpha 2-macroglobulin (alpha 2M) has been shown to inhibit beta-nerve growth factor (NGF)-promoted neurite outgrowth and the survival of embryonic sensory and forebrain neurons, whereas normal alpha 2M has little or no such activity. The objective of this study is to elucidate the mechanism of inhibition by monoamine-activated alpha 2M. Methylamine-activated alpha 2M (MA-alpha 2M) and serotonin-activated alpha 2M (5HT-alpha 2M) dose dependently inhibit NGF-promoted neurite outgrowth of the pheochromocytoma PC12 cell and its subline PC12(6-24) which overexpresses human trk protooncogene product, but have no effect on their viability, and this inhibition can be blocked by high concentrations of NGF. The binding of MA-alpha 2M to trk, which is a part of high-affinity NGF receptor, was studied with PC12(6-24) cells and NIH-3T3 fibroblasts expressing trk (trk-3T3). In each case MA-alpha 2M readily forms stable complexes with trk in vivo, whereas normal alpha 2M does not. Both 5HT-alpha 2M and MA-alpha 2M also dose dependently block NGF-promoted autophosphorylation of trk in vivo, whereas normal alpha 2M and plasmin-reacted alpha 2M are inactive or much less active. MA-alpha 2M also blocks NGF-promoted incorporation of 32P from [32P]ATP into trk receptors in vitro. Neither MA-alpha 2M, 5HT-alpha 2M, nor normal alpha 2M, however, blocks either platelet-derived growth factor-stimulated or epidermal growth factor-stimulated tyrosine phosphorylation of the respective receptors. Tyrosine phosphorylation of two of the intracellular substrates, phospholipase C-gamma 1 and extracellular signal-regulated kinase-2, in the NGF-promoted pathways is also dose dependently blocked by MA-alpha 2M. However, by comparison MA-alpha 2M is more effective in inhibiting the activation of phospholipase C-gamma 1 than trk. We conclude that monoamine-activated alpha 2M may block neurite outgrowth and neuronal survival by its specific binding to NGF receptors, thus inhibiting the NGF-promoted activation of intracellular second messenger pathways.
 ...
PMID:Monoamine-activated alpha 2-macroglobulin binds trk receptor and inhibits nerve growth factor-stimulated trk phosphorylation and signal transduction. 750 36