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In vitro evidence that KLK14 regulates the components of the HGF/Met axis, pro-HGF and HGF-activator inhibitor 1A and 1B.
Biol Chem 2016; 397(12):1299-1305BC

Abstract

Kallikrein-related peptidase (KLK) 14 is a serine protease linked to several pathologies including prostate cancer. We show that KLK14 has biphasic effects in vitro on activating and inhibiting components of the prostate cancer associated hepatocyte growth factor (HGF)/Met system. At 5-10 nm, KLK14 converts pro-HGF to the two-chain heterodimer required for Met activation, while higher concentrations degrade the HGF α-chain. HGF activator-inhibitor (HAI)-1A and HAI-1B, which inhibit pro-HGF activators, are degraded by KLK14 when protease:inhibitor stoichiometry is 1:1 or the protease is in excess. When inhibitors are in excess, KLK14 generates HAI-1A and HAI-1B fragments known to inhibit pro-HGF activating serine proteases. These in vitro data suggest that increased KLK14 activity could contribute at multiple levels to HGF/Met-mediated processes in prostate and other cancers.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27533117

Citation

Reid, Janet C., et al. "In Vitro Evidence That KLK14 Regulates the Components of the HGF/Met Axis, pro-HGF and HGF-activator Inhibitor 1A and 1B." Biological Chemistry, vol. 397, no. 12, 2016, pp. 1299-1305.
Reid JC, Bennett NC, Stephens CR, et al. In vitro evidence that KLK14 regulates the components of the HGF/Met axis, pro-HGF and HGF-activator inhibitor 1A and 1B. Biol Chem. 2016;397(12):1299-1305.
Reid, J. C., Bennett, N. C., Stephens, C. R., Carroll, M. L., Magdolen, V., Clements, J. A., & Hooper, J. D. (2016). In vitro evidence that KLK14 regulates the components of the HGF/Met axis, pro-HGF and HGF-activator inhibitor 1A and 1B. Biological Chemistry, 397(12), pp. 1299-1305. doi:10.1515/hsz-2016-0163.
Reid JC, et al. In Vitro Evidence That KLK14 Regulates the Components of the HGF/Met Axis, pro-HGF and HGF-activator Inhibitor 1A and 1B. Biol Chem. 2016 12 1;397(12):1299-1305. PubMed PMID: 27533117.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vitro evidence that KLK14 regulates the components of the HGF/Met axis, pro-HGF and HGF-activator inhibitor 1A and 1B. AU - Reid,Janet C, AU - Bennett,Nigel C, AU - Stephens,Carson R, AU - Carroll,Melanie L, AU - Magdolen,Viktor, AU - Clements,Judith A, AU - Hooper,John D, PY - 2016/04/01/received PY - 2016/08/10/accepted PY - 2016/8/18/pubmed PY - 2017/7/6/medline PY - 2016/8/18/entrez SP - 1299 EP - 1305 JF - Biological chemistry JO - Biol. Chem. VL - 397 IS - 12 N2 - Kallikrein-related peptidase (KLK) 14 is a serine protease linked to several pathologies including prostate cancer. We show that KLK14 has biphasic effects in vitro on activating and inhibiting components of the prostate cancer associated hepatocyte growth factor (HGF)/Met system. At 5-10 nm, KLK14 converts pro-HGF to the two-chain heterodimer required for Met activation, while higher concentrations degrade the HGF α-chain. HGF activator-inhibitor (HAI)-1A and HAI-1B, which inhibit pro-HGF activators, are degraded by KLK14 when protease:inhibitor stoichiometry is 1:1 or the protease is in excess. When inhibitors are in excess, KLK14 generates HAI-1A and HAI-1B fragments known to inhibit pro-HGF activating serine proteases. These in vitro data suggest that increased KLK14 activity could contribute at multiple levels to HGF/Met-mediated processes in prostate and other cancers. SN - 1437-4315 UR - https://www.unboundmedicine.com/medline/citation/27533117/In_vitro_evidence_that_KLK14_regulates_the_components_of_the_HGF/Met_axis_pro_HGF_and_HGF_activator_inhibitor_1A_and_1B_ L2 - https://www.degruyter.com/doi/10.1515/hsz-2016-0163 DB - PRIME DP - Unbound Medicine ER -