Laminin-3B11, a novel vascular-type laminin capable of inducing prominent lamellipodial protrusions in microvascular endothelial cells.

ABSTRACT: The basement membrane (BM) proteins laminins, which consist of ?, ?, and ? chains, support tissue structures and cellular functions. To date only ?4 and ?5 types of laminins have been identified in the BMs of blood vessels. Our recent study suggested the presence of novel ?3B-containing laminins in vascular BMs. Here we identified and characterized the third member of vascular laminins, laminin-3B11 (Lm3B11). RT-PCR analysis showed that microvascular endothelial (MVE) cells and umbilical vein endothelial cells expressed the messages for the ?3B, ?1, ?2, and ?1 chains. In the culture of MVE cells, ?3B was associated with ?1 and ?1, producing Lm3B11. Recombinant Lm3B11 was overexpressed by introducing the cDNAs of the three chains into HEK-293 cells and purified to homogeneity. Purified Lm3B11 exhibited relatively weak cell adhesion activity through both ?3?1 and ?6?1 integrins. Most characteristically, Lm3B11 strongly stimulated MVE cells to extend many lamellipodial protrusions. This pseudopodial branching was blocked by an inhibitor for Src or phosphatidylinositol 3-kinase. Consistently, Lm3B11 stimulated the phosphorylation of Src and Akt more strongly than other laminins, suggesting that the integrin-derived signaling is mediated by these factors. The unique activity of Lm3B11 appears to be favorable to the branching of capillaries and venules.

SUBMITTER: Mori T 

PROVIDER: S-EPMC2966121 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature