Procollagn C-proteinase and its enhancer protein as regulators of collagen fibril formation and matrix deposition

摘要

Procollagen C-proteinase (PCP) and its enhancer protein (PCPE) are key to collagen fibril-assembly and extracellular matrix formation. PCP cleaves the carboxyl-propeptides of procollagens typos I, II, and lll and this initiates the self assembly of collagen fibrils. PCP can also process pro-lysyl oxidase and laminin 5, and it may cleave the type V procollagen N-propeptides. Procollagen processing by PCP is stimulated by PCPE, a glycoprotein that binds to the C-propeptide of type I procollagen through its N-terminal CUB domains. PCPE is also required for normal cell growth and morphology. Two distinct forms of PCP were isolated from mouse and chick sources. These were recently identified as altematively spliced products of the gene coding for bone morphogenetic protein-l (BMP-l), a member of a family of Zn-dependent astacin-like metalloendopeptidases implicated in tissue patteming and development. Typically, these are multidomain proteases that, in addition to their catalytic domain, contain a number of EGF-like and CUB protein-protein interaction domains. Recent evidence suggests that PCP/BMP-l related proteases can activate TGFp-like growth factors. There is also evidence for additional altematively spliced PCP variants. Thus, PCPs may have important biological functions in addition to their role in collagen fibril assembly.