The Short Arm of Laminin γ2 Chain of Laminin-5 (Laminin-332) Binds Syndecan-1 and Regulates Cellular Adhesion and Migration by Suppressing Phosphorylation of Integrin β4 Chain

The proteolytic processing of laminin-5 at the short arm of the γ2 chain (γ2sa) is known to convert this laminin from a cell adhesion type to a motility type. Here, we studied this mechanism by analyzing the functions of γ2sa. In some immortalized or tumorigenic human cell lines, a recombinant γ2sa, in either soluble or insoluble (coated) form, promoted the adhesion of these cells to the processed laminin-5 (Pr-LN5), and it suppressed their migration stimulated by serum or epidermal growth factor (EGF). γ2sa also suppressed EGF-induced tyrosine phosphorylation of integrin β4 and resultant disruption of hemidesmosome-like structures in keratinocytes. γ2sa bound to syndecan-1, and this binding, as well as its cell adhesion activity, was blocked by heparin. By analyzing the activities of three different γ2sa fragments, the active site of γ2sa was localized to the NH 2 -terminal EGF-like sequence (domain V or LEa). Suppression of syndecan-1 expression by the RNA interference effectively blocked the activities of domain V capable of promoting cell adhesion and inhibiting the integrin β4 phosphorylation. These results demonstrate that domain V of the γ2 chain negatively regulates the integrin β4 phosphorylation, probably through a syndecan-1–mediated signaling, leading to enhanced cell adhesion and suppressed cell motility.