Analyzing the protease web in skin: meprin metalloproteases are activated specifically by KLK4, 5 and 8 vice versa leading to processing of proKLK7 thereby triggering its activation

The metalloproteases meprin alpha and beta are expressed in several tissues, leukocytes, and cancer cells. In skin, meprins are located in separate layers of human epidermis indicating distinct physiological functions, supported by effects on cultured keratinocytes. Meprin beta induces a dramatic ch...

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Bibliographic Details
Published in:Biological chemistry Vol. 391; no. 4; p. 455
Main Authors: Ohler, Anke, Debela, Mekdes, Wagner, Susanne, Magdolen, Viktor, Becker-Pauly, Christoph
Format: Journal Article
Language:English
Published: Germany 01.04.2010
Subjects:
Amino Acid Sequence
Enzyme Activation
Enzyme Precursors - metabolism
Humans
Kallikreins - metabolism
Metalloendopeptidases - chemistry
Metalloendopeptidases - metabolism
Skin - enzymology
Skin - metabolism
Substrate Specificity
ISSN:1437-4315, 1437-4315
Online Access:Get more information
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Summary:The metalloproteases meprin alpha and beta are expressed in several tissues, leukocytes, and cancer cells. In skin, meprins are located in separate layers of human epidermis indicating distinct physiological functions, supported by effects on cultured keratinocytes. Meprin beta induces a dramatic change in cell morphology and a significant reduction in cell number, whereas in vitro evidence suggests a role for meprin alpha in basal keratinocyte proliferation. Meprins are secreted as zymogens that are activated by tryptic proteolytical processing. Here, we identify human kallikrein-related peptidases (KLKs) 4, 5, and 8 to be specific activators of meprins. KLK5 is capable of activating both metalloproteases. Interestingly, KLK4 and 8 cleave off the propeptide of meprin beta only, whereas in contrast plasmin exclusively transforms meprin alpha to its mature form. Moreover, we show that proKLK7 is processed by meprins. N-terminal sequencing revealed cleavage by meprin beta two amino acids N-terminal to mature KLK7. Interestingly, this triggering led to an accelerated activation of the serine protease in the presence of trypsin, but not of other tryptic KLKs, such as KLK2, 4, 5, 8, or 11. In summary, we demonstrate a specific interaction between meprin metalloproteases and kallikrein-related peptidases, revealing possible interactions within the proteolytic web.
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ISSN:1437-4315
1437-4315
DOI:10.1515/BC.2010.023