Cysteine array matrix metalloproteinase (CA-MMP)/MMP-23 is a type II transmembrane matrix metalloproteinase regulated by a single cleavage for both secretion and activation
Dq. Pei et al., Cysteine array matrix metalloproteinase (CA-MMP)/MMP-23 is a type II transmembrane matrix metalloproteinase regulated by a single cleavage for both secretion and activation, J BIOL CHEM, 275(43), 2000, pp. 33988-33997
Matrix metalloproteinases characterized so far are either secreted or membr
ane anchored via a type I transmembrane domain or a glycosylphosphatidylino
sitol linkage. Lacking either membrane-anchoring mechanism, the newly disco
vered CA-MMP/MMP-23 was reported to be expressed as a cell-associated prote
in. In this report, we present evidence that CA-MMP is expressed as an inte
gral membrane zymogen with an N-terminal signal anchor, and secreted as a f
ully processed mature enzyme. We further demonstrate that L(20)GAALSGLCLLSA
LALL(36) is required for this unique membrane localization as a signal anch
or and its secretion is regulated by a proprotein convertase motif RRRR79 s
andwiched between its pro- and catalytic domains. Thus, CA-MMP is a type II
transmembrane MMP that can be regulated by a single proteolytic cleavage f
or both activation and secretion, establishing a novel paradigm for protein
trafficking and processing within the secretory pathway.