Biological Activities of Homologous Loop Regions in the Laminin α Chain G Domains

Abstract

Laminin α chains (α1–α5 chains) have diverse chain-specific biological functions. The LG4 modules of laminin α chains consist of a 14-stranded β-sheet (A-N) sandwich structure. Several biologically active sequences have been identified in the connecting loop regions. Here, we evaluated the biological activities of the loop regions of the E and F strands in the LG4 modules using five homologous peptides from each of the mouse α chains (EF-1: DYATLQLQEGRLHFMFDLG, α1 chain 2747–2765; EF-2: DFGTVQLRNGFPFFSYDLG, α2 chain 2808–2826; EF-3: RDSFVALYLSEGHVIFALG, α3 chain 2266–2284; EF-4: DFMTLFLAHGRLVFMFNVG, α4 chain 1511–1529; EF-5: SPSLVLFLNHGHFVAQTEGP, α5 chain 3304–3323). These homologous peptides showed chain-specific cell attachment and neurite outgrowth activities. Well organized actin stress fibers and focal contacts with vinculin accumulation were observed in fibroblasts attached on EF-1, whereas fibroblasts on EF-2 and EF-4 showed filopodia with ruffling. Fibroblast attachment to EF-2 and EF-4 was mediated by syndecan-2. In contrast, EF-1 promoted α2β1 integrin-mediated fibroblast attachment and inhibited fibroblast attachment to a recombinant laminin α1 chain LG4-5. The receptors for EF-3 and EF-5 are unknown. Further, when the active core sequence of EF-1 was cyclized, utilizing two additional cysteine residues at both the N and C termini through a disulfide bridge, the cyclic peptide significantly enhanced integrin-mediated cell attachment. These results indicate that integrin-mediated cell attachment to the EF-1 sequence is conformation-dependent and that the loop structure is important for the activity. The homologous peptides, which promote either integrin- or syndecan-mediated cell attachment, may be useful for understanding the cell type- and chain-specific biological activities of the laminins. Laminin α chains (α1–α5 chains) have diverse chain-specific biological functions. The LG4 modules of laminin α chains consist of a 14-stranded β-sheet (A-N) sandwich structure. Several biologically active sequences have been identified in the connecting loop regions. Here, we evaluated the biological activities of the loop regions of the E and F strands in the LG4 modules using five homologous peptides from each of the mouse α chains (EF-1: DYATLQLQEGRLHFMFDLG, α1 chain 2747–2765; EF-2: DFGTVQLRNGFPFFSYDLG, α2 chain 2808–2826; EF-3: RDSFVALYLSEGHVIFALG, α3 chain 2266–2284; EF-4: DFMTLFLAHGRLVFMFNVG, α4 chain 1511–1529; EF-5: SPSLVLFLNHGHFVAQTEGP, α5 chain 3304–3323). These homologous peptides showed chain-specific cell attachment and neurite outgrowth activities. Well organized actin stress fibers and focal contacts with vinculin accumulation were observed in fibroblasts attached on EF-1, whereas fibroblasts on EF-2 and EF-4 showed filopodia with ruffling. Fibroblast attachment to EF-2 and EF-4 was mediated by syndecan-2. In contrast, EF-1 promoted α2β1 integrin-mediated fibroblast attachment and inhibited fibroblast attachment to a recombinant laminin α1 chain LG4-5. The receptors for EF-3 and EF-5 are unknown. Further, when the active core sequence of EF-1 was cyclized, utilizing two additional cysteine residues at both the N and C termini through a disulfide bridge, the cyclic peptide significantly enhanced integrin-mediated cell attachment. These results indicate that integrin-mediated cell attachment to the EF-1 sequence is conformation-dependent and that the loop structure is important for the activity. The homologous peptides, which promote either integrin- or syndecan-mediated cell attachment, may be useful for understanding the cell type- and chain-specific biological activities of the laminins. Laminins, multifunctional glycoproteins of basement membranes, have diverse biological activities, including promotion of cell adhesion, migration, neurite outgrowth, tumor metastasis, and angiogenesis (1Colognato H. Yurchenco P.D. Dev. Dyn. 2000; 218: 213-234Crossref PubMed Scopus (1050) Google Scholar). Laminins consist of three different subunits, α, β, and γ chains. So far, five α, three β, and three γ chains have been identified, and at least 15 isoforms (laminin-1 to -15) are formed by various combinations of each subunit (2Burgeson R.E. Chiquet M. Deutzmann R. Ekblom P. Engel J. Kleinman H.K. Martin G.R. Meneguzzi G. Paulson M. Sanes J. Timpl R. Tryggvason K. Yamada Y. Yurchenco P.D. Matrix Biol. 1994; 14: 209-211Crossref PubMed Scopus (696) Google Scholar, 3Miner J.H. Patton B.L. Lentz S.I. Gilbert D.J. Snider W.D. Jenkins N.A. Copeland N.G. Sanes J.R. J. Cell Biol. 1997; 137: 685-701Crossref PubMed Scopus (582) Google Scholar, 4Iivanainen A. Morita T. Tryggvason K. J. Biol. 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Matrix Biol. 2000; PubMed Scopus Google Scholar). Several have on the biological activities of the α1 chain a proteolytic the modules of the α1 cell activity mediated through A. M. Timpl R. J. Cell Biol. PubMed Scopus Google Scholar, A. M. Timpl R. Ekblom P. J. Cell Biol. PubMed Scopus Google Scholar). and with the α1 chain have that activity is on protein Yurchenco P.D. J. Cell Biol. PubMed Scopus (102) Google Scholar, P.D. J. Biol. Chem. Full Text PDF PubMed Google Scholar). Several synthetic peptides from the α1 chain promote cell adhesion, neurite outgrowth, and tumor and (8Nomizu M. Kim W.H. Yamamura K. Utani A. Song S.Y. Otaka A. Roller P.P. Kleinman H.K. Yamada Y. J. Biol. Chem. 1995; 270: 20583-20590Abstract Full Text Full Text PDF PubMed Scopus (240) Google Scholar, B.L. M. Yamada Y. Kleinman H.K. Cell PubMed Scopus Google Scholar, S.Y. M. Yamada Y. Kleinman H.K. J. 1997; PubMed Scopus Google Scholar, W.H. M. Song S.Y. K. Kuratomi Y. Kleinman H.K. Yamada Y. 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Yamada Y. Kleinman H.K. Ponce M.L. J. 1999; PubMed Scopus Google Scholar). active in the of the α chains have to be identified A. M. H. K. T. H. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, K. Utani A. M. Yamada M. H. H. M. PubMed Scopus Google Scholar, H. H. H. M. K. Y. J. Biol. Chem. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, Utani A. H. H. H. Y. M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, Hoffman M.P. H. M. M. Yamada Y. J. Biol. Chem. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, M. M. Otaka A. Yamada Y. M. Cell PubMed Scopus Google Scholar). The laminin α3 chain promoted and cell attachment and neurite outgrowth A. M. H. K. T. H. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, K. Utani A. M. Yamada M. H. H. M. PubMed Scopus Google Scholar). The mouse laminin α4 chain sequence showed and cell attachment activity H. H. H. M. K. Y. J. Biol. Chem. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, Utani A. H. H. H. Y. M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). These active sequences are in the homologous of the LG4 modules of the α3 and α4 chains. The structure of the laminin α2 has been and to consist of strands Timpl R. 1999; 4: Full Text Full Text PDF PubMed Scopus Google Scholar). The homologous regions of and are on the connecting loop the E and F strands R. T. Matrix Biol. 2000; PubMed Scopus Google Scholar, A. M. H. K. T. H. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, K. Utani A. M. Yamada M. H. H. M. PubMed Scopus Google Scholar, Utani A. H. H. H. Y. M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). using recombinant LG4 with or of residues and laminin α3 and mouse laminin α4 in the loop regions that the loop regions are for the biological activity of the recombinant A. M. H. K. T. H. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, H. H. H. M. K. Y. J. Biol. Chem. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). In we on the loop regions of laminin α chain LG4 five homologous peptides to from the LG4 modules of the α chains and evaluated biological activity. These peptides showed chain-specific cell attachment activity with different including and and of the peptides promoted neurite Further, a of the which with α2β1 enhanced the biological activity. peptides were using and in the M. Kuratomi Y. Malinda M.K. Song S.Y. Miyoshi K. Otaka A. Powel S.K. Hoffman M.P. Kleinman H.K. Yamada Y. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus (137) Google Scholar). and were from and The were in a using or was the a was and for of N in was The chain were and and or and The peptide were and from the using a at for The peptides were and with and by using a and a of cyclic was using the synthetic with the was a the was with peptide were on by the peptide of the peptide with a of at for a which was with The peptide was by in a of at for and by using a with a of and of the peptides were by and by a and of or of a for of a recombinant mouse laminin α1 chain and of were using for the of recombinant laminin α3 chain A. M. H. K. T. H. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, K. Utani A. M. Yamada M. H. H. M. PubMed Scopus Google Scholar). The H. H. H. M. K. Y. J. Biol. Chem. 2000; Full Text Full Text PDF PubMed Scopus Google that the mouse laminin α1 chain a from was a in the chain to the α1 chain The with the were of the mouse laminin α1 of the mouse laminin α1 The of the mouse laminin α1 chain were the which the laminin and the sequences in the A. M. H. K. T. H. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). The was to with the with in was for at and was The was to a protein in and the protein was with and by The was to using a The protein was with and in was with the was from α1 α2 α3 and were from chain was from and fibroblasts P. PubMed Scopus Google K. M. T. PubMed Scopus Google and K. H. K. H. J. A. 1995; Google were in and and were in the of A. M. H. K. T. H. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). A. PubMed Scopus Google were in and The were at in a Cell attachment were in with either various of synthetic peptides or the peptide various of peptides in of were to the and at various of in of were to the and at The were with of in at for and with were with and with at for with were to the and at for The attached were with in for with was to the and the at was using a of cell attachment with and peptides, fibroblasts were for at in the of either or various of of cell attachment with fibroblasts were in with of the for 15 at the were to the and for at were neurite outgrowth a was with the of peptides with for were with and the in The were at for in The were and with a in for the were the were analyzed a and of of peptides in of were on a and at The were by the of in for and with in fibroblasts were and at for were with in with in for and with mouse vinculin to with in and actin were for with a of mouse and to and with in which for with the were with and were with a and using of was with Cell and of homologous peptides to from mouse laminin α chains (α1–α5 chains) were on the of the LG4 modules R. T. Matrix Biol. 2000; PubMed Scopus Google These peptides the E and F β-sheet strands and connecting loop regions. we cell attachment activity using and and a cell-adhesive peptide from the laminin α1 chain was a (8Nomizu M. Kim W.H. Yamamura K. Utani A. Song S.Y. Otaka A. Roller P.P. Kleinman H.K. Yamada Y. J. Biol. Chem. 1995; 270: 20583-20590Abstract Full Text Full Text PDF PubMed Scopus (240) Google Scholar). EF-2 α2 chain and EF-4 α4 chain showed cell attachment activity with of the cell EF-1 α1 chain promoted fibroblast and attachment, whereas activity was observed with the EF-5 α5 chain promoted fibroblast attachment was with the cell EF-3 α3 chain showed cell attachment activity with of the of the homologous loop regions in the laminin α chain cell attachment various of peptides were on and and were In the biological activities of the peptides were and evaluated to observed with Cell attachment was evaluated on the with on with that on neurite outgrowth with various of peptides were on the and outgrowth was evaluated on the promote neurite and vinculin were in the fibroblasts attached on peptides and of focal contacts was evaluated on the focal observed and vinculin were in the fibroblasts attached on peptides and of focal contacts was evaluated on the focal observed cell attachment fibroblasts were in the of or and for cell attachment to EF-1, and which were inhibited by or were which enhanced cell attachment to EF-2 and and inhibited cell attachment to EF-1 α1 chain was a cell attachment various of peptides were on and and were In the biological activities of the peptides were and evaluated to observed with Cell attachment was evaluated on the with on with that on neurite outgrowth with various of peptides were on the and outgrowth was evaluated on the promote neurite and vinculin were in the fibroblasts attached on peptides and of focal contacts was evaluated on the focal and vinculin were in the fibroblasts attached on peptides and of focal contacts was evaluated on the focal cell attachment fibroblasts were in the of or and for cell attachment to EF-1, and which were inhibited by or were which enhanced cell attachment to EF-2 and and inhibited cell attachment to α1 chain (8Nomizu M. Kim W.H. Yamamura K. Utani A. Song S.Y. Otaka A. Roller P.P. Kleinman H.K. Yamada Y. J. Biol. Chem. 1995; 270: 20583-20590Abstract Full Text Full Text PDF PubMed Scopus (240) Google was a in a attachment activity of the cell attachment of fibroblast and were with various of peptides, and were to the for with the attached were in and the was of fibroblasts on the of a were with of EF-1 EF-2 EF-4 and and of EF-5 were to the a attached were with were with a on a The of fibroblasts on the peptides the fibroblasts were with Y. Y. K. Yamada M. T. M. J. PubMed Scopus Google Scholar). EF-1 promoted fibroblast whereas the on EF-2 and EF-4 showed to that on and on EF-5 attached and showed a to both EF-1 and we the neurite outgrowth activity of five peptides with EF-4 and EF-3 promoted neurite outgrowth with C and whereas EF-1, and EF-5 activity and These results that the homologous peptides have cell cell attachment and neurite outgrowth activities. of and of we on the EF-1, and EF-5 peptides, which promoted fibroblast attachment, and the of actin and of vinculin on the the actin were with Y. Y. K. Yamada M. T. M. J. PubMed Scopus Google and focal contacts with vinculin were observed The EF-1 peptide organized actin stress fibers and focal contacts vinculin In contrast, EF-2 and EF-4 a to with filopodia and and focal was observed and EF-5 actin stress fibers or focal contacts These results that the to the peptides are of and on Fibroblast we evaluated the of and on fibroblast attachment to the peptides and laminin-1 for and cell attachment, inhibited attachment on EF-2 and whereas cell attachment on EF-1 and EF-5 was inhibited by In contrast, significantly inhibited cell attachment on EF-1, on and on attachment was Further, fibroblast attachment to EF-5 was enhanced by attached to the EF-1 peptide in a that EF-1 promoted integrin-mediated cell cell attachment on EF-2 and EF-4 was inhibited by that peptides have the to with of with or to and are cell fibroblasts on and A. M. H. K. T. H. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). was in cell to EF-2 and we and A. M. H. K. T. H. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google and analyzed cell attachment cell to EF-2 and EF-4 was significantly enhanced by of and enhanced by of of either on cell attachment to These results indicate that cell attachment to EF-2 and EF-4 syndecan-2. of on Cell to EF-1 promoted fibroblast attachment, we the of subunit on fibroblast attachment to EF-1 Cell attachment to EF-1 was significantly inhibited by and These cell attachment to EF-2 including and cell attachment to The indicate that the EF-1 peptide α2β1 integrin-mediated cell attachment. Cell of a Laminin α1 and of the EF-1 on the of the laminin α1 chain the EF-1 sequence with α2β1 was we a recombinant laminin α1 chain and integrin-mediated cell attachment to the attached to in a inhibited of the attachment that cell chains are in the fibroblast attachment to inhibited of the cell attachment, that a of the cell attachment was mediated by including subunit inhibited fibroblast attachment to whereas subunit The of inhibited of fibroblast attachment to laminin-1 Fibroblast attachment to was inhibited in the of both and The EF-1 peptide was to attachment to the recombinant protein with α2β1 and with cell are in fibroblast attachment to the laminin α1 chain and the EF-1 is important for the with α2β1 of the active core sequence of EF-1, we and peptides and cell attachment activity using fibroblasts peptide of EF-1, with whereas the activity of with a of the and residues from was that of the or were from a in cell attachment activity was Further, the of from in of activity. a peptide of EF-1, whereas the activity of with a of the from showed activity. and peptide of EF-1, showed cell attachment activity. These results that the sequence is for the cell attachment activity of The of the activity of may be to which are by the additional attachment activity of and cyclic peptides of of the synthetic peptides are in the peptides have The the attachment was on the cell attachment with that on with that on core sequences are in of the synthetic peptides are in the peptides have The the was on the cell attachment with that on with that on core sequences are in in a EF-1 and sequences the residues were the were with residues in the EF-1 and and promoted fibroblast attachment EF-1 and Cell of we a cyclic peptide to the of in the biological The peptide significantly enhanced fibroblast attachment activity to the Fibroblast attached on showed organized actin stress fibers and focal contacts Further, fibroblast attachment to was significantly inhibited by and by and whereas the and fibroblast attachment. These results indicate that the peptide with α2β1 to that of a peptide of on Cell to the EF-1 we the of various peptides on fibroblast attachment The EF-1 peptide showed inhibited cell attachment. The peptide inhibited fibroblast attachment to EF-1 to the peptide from that with (8Nomizu M. Kim W.H. Yamamura K. Utani A. Song S.Y. Otaka A. Roller P.P. Kleinman H.K. Yamada Y. J. Biol. Chem. 1995; 270: 20583-20590Abstract Full Text Full Text PDF PubMed Scopus (240) Google Scholar, J. Biol. Chem. Full Text PDF PubMed Google cell attachment. The that peptide is important for the the EF-1 sequence and α2β1 and that the is Previously, we identified the and sequences cell attachment and in the of the laminin α3 and the mouse laminin α4 A. M. H. K. T. H. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, K. Utani A. M. Yamada M. H. H. M. PubMed Scopus Google Scholar, H. H. H. M. K. Y. J. Biol. Chem. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, Utani A. H. H. H. Y. M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). on the of the LG4 the and sequences are homologous in the connecting loop the E and F strands R. T. Matrix Biol. 2000; PubMed Scopus Google Scholar, Timpl R. 1999; 4: Full Text Full Text PDF PubMed Scopus Google Scholar). using recombinant LG4 with or of residues and laminin α3 and mouse laminin α4 in the loop regions has that the loop regions are for biological activity of the recombinant A. M. H. K. T. H. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, H. H. H. M. K. Y. J. Biol. Chem. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). Here, we have five homologous peptides to from the loop regions of mouse laminin chain LG4 The peptides showed and cell cell attachment and neurite outgrowth activity. EF-2 and EF-4 promoted cell attachment of of the cell These results indicate that the loop in the α2 and α4 chains may a in diverse are EF-1 showed cell attachment activity with fibroblasts and whereas EF-5 promoted fibroblast attachment. The α1 and α5 chains are in the and in diverse (1Colognato H. Yurchenco P.D. Dev. Dyn. 2000; 218: 213-234Crossref PubMed Scopus (1050) Google Scholar). may with with the loop in Further, promoted neurite outgrowth on EF-3 and Laminin α chains are in various (1Colognato H. Yurchenco P.D. Dev. Dyn. 2000; 218: 213-234Crossref PubMed Scopus (1050) Google Scholar, A. M.F. Meneguzzi G. Cell 1994; PubMed Scopus Google Scholar). is that the loop regions in the α3 and α4 chains are important for the with whereas the may in the and α5 chains. a of with and various A. J.R. Curr. Opin. Cell Biol. PubMed Scopus Google Scholar, M. A. PubMed Scopus Google Scholar). Previously, we the a and in fibroblasts A. M. H. K. T. H. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google and the sequence a in M.P. J. M. Yamada Y. Kleinman H.K. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, M.P. M. Yamada Y. Kleinman H.K. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). In syndecan-mediated cell attachment to the of and to the actin were with and focal contacts with vinculin accumulation were observed Y. Y. K. Yamada M. T. M. J. PubMed Scopus Google Scholar, Biol. 1999; PubMed Scopus Google Scholar). In actin and vinculin of fibroblasts on EF-2 and EF-4 were to that on cell attachment to EF-2 and EF-4 was inhibited by and was significantly enhanced by of syndecan-2. These results that cell attachment to EF-2 and to EF-4 is mediated by syndecan-2. are important cell receptors for laminins. Several in laminin-1 have been The to modules in the α1 chain are a for and (1Colognato H. Yurchenco P.D. Dev. Dyn. 2000; 218: 213-234Crossref PubMed Scopus (1050) Google Scholar). α2β1 is a for and laminin J. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, J. Cell Biol. PubMed Scopus Google Scholar, H. M. Yurchenco P.D. J. Biol. Chem. 1997; 272: Full Text Full Text PDF PubMed Scopus Google Scholar). of the laminin α1 with and α2β1 H. M. Yurchenco P.D. J. Biol. Chem. 1997; 272: Full Text Full Text PDF PubMed Scopus Google Scholar, H. Yamada Y. Yurchenco P.D. J. Biol. Chem. 1995; 270: Full Text Full Text PDF PubMed Scopus Google Scholar). observed actin stress and focal contacts in fibroblasts on Further, fibroblast attachment to the EF-1 peptide was inhibited by and The EF-1 is in the α1 chain LG4 The which is laminin-1 that the α1 chain has and activities (1Colognato H. Yurchenco P.D. Dev. Dyn. 2000; 218: 213-234Crossref PubMed Scopus (1050) Google Scholar, R. T. Matrix Biol. 2000; PubMed Scopus Google Scholar). The and α2β1 has been The subunit mediated and cell attachment to A. M. Timpl R. J. Cell Biol. PubMed Scopus Google Scholar). a recombinant α1 chain and observed α2β1 integrin-mediated fibroblast attachment to the the EF-1 peptide inhibited fibroblast attachment to EF-1 is a peptide with α2β1 and sequence in the laminin α1 chain is a α2β1 in The peptide mouse laminin α1 chain which is from the LG4 and to significantly inhibited cell attachment to the protein and M.P. M. Yamada Y. Kleinman H.K. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). These results that cell and with the laminin α1 chain the and EF-1 that EF-5 showed attachment activity with fibroblasts which was enhanced by and vinculin the fibroblasts on EF-5 from that of or we that mouse laminin α5 chain the EF-5 inhibited and Dev. in Scholar). the homologous peptides of from the α1 chain were Further, the of by in a different from that observed with a peptide from the laminin α1 chain Y. M. Yamada Y. Dev. Dyn. 1998; PubMed Scopus Google Scholar). These results that the EF-5 may with different in α5 chain-specific biological activity. EF-3 promoted neurite outgrowth with Previously, we that a recombinant laminin α3 chain LG4 and a on the loop of the promote neurite outgrowth with K. Utani A. M. Yamada M. H. H. M. PubMed Scopus Google Scholar). The peptide inhibited cell attachment to the recombinant laminin α3 chain LG4 K. Utani A. M. Yamada M. H. H. M. PubMed Scopus Google Scholar). These results indicate that of the α3 chain is important for neurite Previously, cell-adhesive peptides were and showed biological activity cyclic peptide enhanced cell attachment activity and showed of tumor that observed with peptide H.K. J. Y. M. Yamada Y. Martin G.R. 272: PubMed Scopus Google Scholar). peptides showed in activity M. M. G. J. Timpl R. H. 1991; PubMed Scopus Google Scholar). cyclic peptides with different including and M. K. M. G. H. Timpl R. Engel J. J. Biol. Chem. 1994; Full Text PDF PubMed Google Scholar). In of the peptide significantly enhanced cell attachment activity and the on cell attachment to The peptide actin stress and focal and with α2β1 to These results indicate that of the EF-1 sequence is enhanced by the the cyclic in the EF-4 significantly and cell attachment activity when with the T. A. A. and M. the loop of the regions is for to Here, we the biological activities of five homologous peptides from the loop regions of the laminin α chain LG4 These homologous peptides showed chain-specific cell attachment and neurite outgrowth activities and with different cell α2β1 and syndecan-2. These results that the loop regions are important in various biological activities of the laminin isoforms in