title: The short arm of laminin gamma2 chain of laminin-5 (laminin-332) binds syndecan-1 and regulates cellular adhesion and migration by suppressing phosphorylation of integrin beta4 chain.
abstract: The proteolytic processing of laminin-5 at the short arm of the gamma2 chain (gamma2sa) 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 gamma2sa. In some immortalized or tumorigenic human cell lines, a recombinant gamma2sa, 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). Gamma2sa also suppressed EGF-induced tyrosine phosphorylation of integrin beta4 and resultant disruption of hemidesmosome-like structures in keratinocytes. Gamma2sa 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 gamma2sa fragments, the active site of gamma2sa 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 beta4 phosphorylation. These results demonstrate that domain V of the gamma2 chain negatively regulates the integrin beta4 phosphorylation, probably through a syndecan-1-mediated signaling, leading to enhanced cell adhesion and suppressed cell motility.
authors.affiliation: Division of Cell Biology, Kihara Institute for Biological Research, Yokohama City University, Yokohama 244-0813, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ogawa
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tsubota
authors.forename: Junko
authors.initials: J
authors.lastname: Hashimoto
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kariya
authors.forename: Kaoru
authors.initials: K
authors.lastname: Miyazaki
mesh_terms: D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D018076:DNA, Complementary / Q000235:genetics; D004815:Epidermal Growth Factor / Q000494:pharmacology; D022002:Hemidesmosomes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D039663:Integrin beta4 / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D053668:Syndecan-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000097794:Kalinin
chemical_list: D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; D004815:Epidermal Growth Factor; D039663:Integrin beta4; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D053668:Syndecan-1; D000097794:Kalinin; C508241:SDC1 protein, human