Regulation of biological activity of laminin-5 by proteolytic processing of γ2 chain

• Published in: Journal of cellular biochemistry Vol. 92; no. 4; pp. 701 - 714
• Main Authors: Ogawa, Takashi, Tsubota, Yoshiaki, Maeda, Masato, Kariya, Yoshinobu, Miyazaki, Kaoru
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.07.2004
• Subjects: cell adhesion; cell migration; laminin-5; processing; proteinase
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.20112

Laminin‐5 (LN5), which regulates both cell adhesion and cell migration, undergoes specific extracellular proteolytic processing at an amino‐terminal region of the γ2 chain as well as at a carboxyl‐terminal region of the α3 chain. To clarify the biological effect of the γ2 chain processing, we prepared a human recombinant LN5 with the 150‐kDa, non‐processed γ2 chain (GAA‐LN5) and natural LN5 with the 105‐kDa, processed γ2 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 γ2 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 γ2 chain is more adherent but less migratory than the carcinoma cells expressing a mixture of LN5 forms with the processed γ2 chain and with the unprocessed one. The functional change of LN5 by the proteolytic processing of the γ2 chain may contribute to elevated cell migration under some pathological conditions such as wound healing and tumor invasion. © 2004 Wiley‐Liss, Inc.