title: The potential of laminin-2-biomimetic short peptide to promote cell adhesion, spreading and migration by inducing membrane recruitment and phosphorylation of PKCδ.
abstract: Laminin α2 chain plays an important role in basement membrane assembly and peripheral myelinogenesis; however, the integrin binding motif within human laminin α2 chain and the signaling pathways downstream of this ligand-receptor interaction are poorly understood. We identified a motif, RNIPPFEGCIWN (Ln2-LG3-P2), within LG3 domain of human laminin α2 chain as a major site for both α3β1 integrin and cellular activities such as cell adhesion, spreading, and migration. Binding of α3β1 integrin with Ln2-LG3-P2 induced the membrane recruitment of protein kinase Cδ (PKCδ) and stimulated its tyrosine phosphorylation. The cellular activities induced by Ln2-LG3-P2 and the phosphorylation of focal adhesion kinase (FAK) were inhibited by rottlerin, a PKCδ inhibitor, but not by Gö6976, a PKCα/β inhibitor. These results indicate that RNIPPFEGCIWN motif within human laminin α2 chain is a major ligand for α3β1 integrin, and that binding of α3β1 integrin mediates cellular activities through membrane recruitment and tyrosine phosphorylation of PKCδ and FAK phosphorylation.
authors.affiliation: Department of Oral Biochemistry and Program in Cancer and Developmental Biology, Dental Research Institute, Seoul National University School of Dentistry, 28 Yeonkun-Dong, Chongno-Ku, Seoul 110-749, Republic of Korea. jsy1618@snu.ac.kr
authors.forename: Sung Youn
authors.initials: SY
authors.lastname: Jung
authors.forename: Jin-Man
authors.initials: JM
authors.lastname: Kim
authors.forename: Seung-Ki
authors.initials: SK
authors.lastname: Min
authors.forename: O Bok
authors.initials: OB
authors.lastname: Kim
authors.forename: Da Hyun
authors.initials: DH
authors.lastname: Jang
authors.forename: Hyun Ki
authors.initials: HK
authors.lastname: Kang
authors.forename: Byung-Moo
authors.initials: BM
authors.lastname: Min
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000378:metabolism; D040761:Biomimetic Materials / Q000737:chemistry / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology*; D002465:Cell Movement / Q000187:drug effects*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D022001:Focal Adhesions / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D039201:Integrin alpha3beta1 / Q000378:metabolism; D007797:Laminin / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008969:Molecular Sequence Data; D016716:PC12 Cells; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D051745:Protein Kinase C-delta / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D022502:Stress Fibers / Q000187:drug effects / Q000378:metabolism
chemical_list: D039201:Integrin alpha3beta1; D007797:Laminin; D010455:Peptides; D019000:Phosphotyrosine; D001120:Arginine; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051745:Protein Kinase C-delta