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 gamma 2 chain (gamma 2sa) 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 gamma 2sa. In some immortalized or tumorigenic human cell lines, a recombinant gamma 2sa, 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). gamma 2sa also suppressed EGF-induced tyrosine phosphorylation of integrin beta 4 and resultant disruption of hemidesmosome-like structures in keratinocytes. gamma 2sa 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 gamma 2sa fragments, the active site of gamma 2sa was localized to the NH2-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 beta 4 phosphorylation. These results demonstrate that domain V of the gamma 2 chain negatively regulates the integrin beta 4 phosphorylation, probably through a syndecan-1-mediated signaling, leading to enhanced cell adhesion and suppressed cell motility.