Regulation of biological activity of laminin-5 by proteolytic processing of gamma2 chain.
Laminin-5 (LN5), which regulates both cell adhesion and cell migration, undergoes specific extracellular proteolytic processing at an amino-terminal region of the gamma2 chain as well as at a carboxyl-terminal region of the alpha3 chain. To clarify the biological effect of the gamma2 chain processing, we prepared a human recombinant LN5 with the 150-kDa, non-processed gamma2 chain (GAA-LN5) and natural LN5 with the 105-kDa, processed gamma2 chain (Nat-LN5). Comparison of their biological activities demonstrated that GAA-LN5 had an about five-times higher cell adhesion activity but an about two-times lower cell migration activity than Nat-LN5. This implies that the proteolytic processing of LN5 gamma2 chain converts the LN5 from the cell adhesion type to the cell migration type. It was also found that human gastric carcinoma cells expressing the LN5 with the non-processed gamma2 chain is more adherent but less migratory than the carcinoma cells expressing a mixture of LN5 forms with the processed gamma2 chain and with the unprocessed one. The functional change of LN5 by the proteolytic processing of the gamma2 chain may contribute to elevated cell migration under some pathological conditions such as wound healing and tumor invasion.
Ogawa
Takashi
T
Division of Cell Biology, Kihara Institute for Biological Research, Yokohama City University, 641-12 Maioka-cho, Totsuka-ku, Yokohama 244-0813, Japan.
Tsubota
Yoshiaki
Y
Maeda
Masato
M
Kariya
Yoshinobu
Y
Miyazaki
Kaoru
K
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002465:Cell Movement; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D007797:Laminin / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured; D000097794:Kalinin
D015815:Cell Adhesion Molecules; D010450:Endopeptidases; D007797:Laminin; D011994:Recombinant Proteins; D000097794:Kalinin; C400567:LAMC2 protein, human