JAM4 enhances hepatocyte growth factor-mediated branching and scattering of Madin-Darby canine kidney cells.

Genes Cells

Department of Medical Biochemistry, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.

Published: September 2004

AI Article Synopsis

  • JAM4 is a member of the immunoglobulin superfamily that plays a role in cell adhesion and signaling at tight junctions in epithelial cells by interacting with MAGI-1.
  • The study created MDCK cells that express JAM4 (MDCK-JAM4), revealing that these cells exhibit increased branching and scattering in response to hepatocyte growth factor (HGF) compared to wild-type MDCK cells.
  • Further investigations showed that JAM4 activates the Rac signaling pathway, leading to the formation of cell protrusions, which suggests that JAM4 enhances Rac activation, contributing to the observed changes in cell morphology.

Article Abstract

Junctional adhesion molecule (JAM) 4 is a member of immunoglobulin superfamily that interacts with MAGI-1, a membrane-associated guanylate kinase protein at tight junctions in epithelial cells. We prepared Madin-Darby canine kidney II (MDCK) cells expressing JAM4 (MDCK-JAM4) and compared them with wild MDCK cells. The treatment of hepatocyte growth factor (HGF) induced more prominent branching and scattering in MDCK-JAM4 cells. Subsequently we attempted to identify signalling pathways modified by JAM4. The over-expression of JAM4 induced the formation of protrusions in COS-7 cells. Although those protrusions were different from typical lamellipodia, the dominant negative mutant of Rac suppressed them. The pull-down assay using CDC42 and Rac interactive binding domain of PAK also supports that Rac is activated in COS-7 cells expressing JAM4. Taken together, JAM4 itself activates Rac and may augment Rac activation by HGF, resulting in the enhancement of branching and scattering.

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http://dx.doi.org/10.1111/j.1365-2443.2004.00765.xDOI Listing

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