Multi-factorial modulation of IGD motogenic potential in MSF (Migration Stimulating Factor)

Ian R. Ellis (Lead / Corresponding author), Sarah J. Jones, David Staunton, Ioannis Vakonakis, David G. Norman, Jennifer R. Potts, Caroline M. Milner, Nicola A. G. Meenan, Sophie Raibaud, Go Ohea, Ana M. Schor, Seth L. Schor

    Research output: Contribution to journalArticle

    8 Citations (Scopus)

    Abstract

    Migration Stimulating Factor (MSF) is a genetically truncated isoform of fibronectin (Fn). MSF is a potent stimulator of fibroblast migration, whereas full length Fn is devoid of motogenic activity. MSF and Fn contain four IGD motifs, located in the 3rd, 5th, 7th and 9th type I modules; these modules are referred to as (3)FnI, (5)FnI, (7)FnI and (9)FnI, respectively. We have previously reported that mutation of IGD motifs in modules (7)FnI and (9)FnI of MSF is sufficient to completely abolish the motogenic response of target adult skin fibroblasts. We now report that the IGD sequences in (3)FnI and (5)FnI are also capable of exhibiting motogenic activity when present within fragments of MSF. When present within (1-5)FnI, these sequences require the presence of serum or vitronectin for their motogenic activity to be manifest, whereas the IGD sequences in (7)FnI and (9)FnI are bioactive in the absence of serum factors. All MSF and IGD-containing peptides stimulated the phosphorylation of the integrin binding protein focal adhesion kinase (FAK) but did not necessarily affect migration. These results suggest that steric hindrance determines the motogenic activity of MSF and Fn, and that both molecules contain cryptic bioactive fragments. (C) 2010 Elsevier Inc. All rights reserved.

    Original languageEnglish
    Pages (from-to)2465-2476
    Number of pages12
    JournalExperimental Cell Research
    Volume316
    Issue number15
    DOIs
    Publication statusPublished - 10 Sep 2010

    Keywords

    • Cell motility
    • Fibronectin
    • Fibroblasts
    • STAPHYLOCOCCUS-AUREUS FNBPA
    • GELATIN-BINDING DOMAIN
    • TANDEM BETA-ZIPPER
    • HUMAN FIBRONECTIN
    • FIBROBLAST MIGRATION
    • CRYSTAL-STRUCTURES
    • CELL MOTILITY
    • MATRIX
    • ADHESION
    • RECEPTOR

    Cite this

    Ellis, Ian R. ; Jones, Sarah J. ; Staunton, David ; Vakonakis, Ioannis ; Norman, David G. ; Potts, Jennifer R. ; Milner, Caroline M. ; Meenan, Nicola A. G. ; Raibaud, Sophie ; Ohea, Go ; Schor, Ana M. ; Schor, Seth L. / Multi-factorial modulation of IGD motogenic potential in MSF (Migration Stimulating Factor). In: Experimental Cell Research. 2010 ; Vol. 316, No. 15. pp. 2465-2476.
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    abstract = "Migration Stimulating Factor (MSF) is a genetically truncated isoform of fibronectin (Fn). MSF is a potent stimulator of fibroblast migration, whereas full length Fn is devoid of motogenic activity. MSF and Fn contain four IGD motifs, located in the 3rd, 5th, 7th and 9th type I modules; these modules are referred to as (3)FnI, (5)FnI, (7)FnI and (9)FnI, respectively. We have previously reported that mutation of IGD motifs in modules (7)FnI and (9)FnI of MSF is sufficient to completely abolish the motogenic response of target adult skin fibroblasts. We now report that the IGD sequences in (3)FnI and (5)FnI are also capable of exhibiting motogenic activity when present within fragments of MSF. When present within (1-5)FnI, these sequences require the presence of serum or vitronectin for their motogenic activity to be manifest, whereas the IGD sequences in (7)FnI and (9)FnI are bioactive in the absence of serum factors. All MSF and IGD-containing peptides stimulated the phosphorylation of the integrin binding protein focal adhesion kinase (FAK) but did not necessarily affect migration. These results suggest that steric hindrance determines the motogenic activity of MSF and Fn, and that both molecules contain cryptic bioactive fragments. (C) 2010 Elsevier Inc. All rights reserved.",
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    author = "Ellis, {Ian R.} and Jones, {Sarah J.} and David Staunton and Ioannis Vakonakis and Norman, {David G.} and Potts, {Jennifer R.} and Milner, {Caroline M.} and Meenan, {Nicola A. G.} and Sophie Raibaud and Go Ohea and Schor, {Ana M.} and Schor, {Seth L.}",
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    Ellis, IR, Jones, SJ, Staunton, D, Vakonakis, I, Norman, DG, Potts, JR, Milner, CM, Meenan, NAG, Raibaud, S, Ohea, G, Schor, AM & Schor, SL 2010, 'Multi-factorial modulation of IGD motogenic potential in MSF (Migration Stimulating Factor)', Experimental Cell Research, vol. 316, no. 15, pp. 2465-2476. https://doi.org/10.1016/j.yexcr.2010.04.003

    Multi-factorial modulation of IGD motogenic potential in MSF (Migration Stimulating Factor). / Ellis, Ian R. (Lead / Corresponding author); Jones, Sarah J.; Staunton, David; Vakonakis, Ioannis; Norman, David G.; Potts, Jennifer R.; Milner, Caroline M.; Meenan, Nicola A. G.; Raibaud, Sophie; Ohea, Go; Schor, Ana M.; Schor, Seth L.

    In: Experimental Cell Research, Vol. 316, No. 15, 10.09.2010, p. 2465-2476.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Multi-factorial modulation of IGD motogenic potential in MSF (Migration Stimulating Factor)

    AU - Ellis, Ian R.

    AU - Jones, Sarah J.

    AU - Staunton, David

    AU - Vakonakis, Ioannis

    AU - Norman, David G.

    AU - Potts, Jennifer R.

    AU - Milner, Caroline M.

    AU - Meenan, Nicola A. G.

    AU - Raibaud, Sophie

    AU - Ohea, Go

    AU - Schor, Ana M.

    AU - Schor, Seth L.

    N1 - MEDLINE® is the source for the MeSH terms of this document.

    PY - 2010/9/10

    Y1 - 2010/9/10

    N2 - Migration Stimulating Factor (MSF) is a genetically truncated isoform of fibronectin (Fn). MSF is a potent stimulator of fibroblast migration, whereas full length Fn is devoid of motogenic activity. MSF and Fn contain four IGD motifs, located in the 3rd, 5th, 7th and 9th type I modules; these modules are referred to as (3)FnI, (5)FnI, (7)FnI and (9)FnI, respectively. We have previously reported that mutation of IGD motifs in modules (7)FnI and (9)FnI of MSF is sufficient to completely abolish the motogenic response of target adult skin fibroblasts. We now report that the IGD sequences in (3)FnI and (5)FnI are also capable of exhibiting motogenic activity when present within fragments of MSF. When present within (1-5)FnI, these sequences require the presence of serum or vitronectin for their motogenic activity to be manifest, whereas the IGD sequences in (7)FnI and (9)FnI are bioactive in the absence of serum factors. All MSF and IGD-containing peptides stimulated the phosphorylation of the integrin binding protein focal adhesion kinase (FAK) but did not necessarily affect migration. These results suggest that steric hindrance determines the motogenic activity of MSF and Fn, and that both molecules contain cryptic bioactive fragments. (C) 2010 Elsevier Inc. All rights reserved.

    AB - Migration Stimulating Factor (MSF) is a genetically truncated isoform of fibronectin (Fn). MSF is a potent stimulator of fibroblast migration, whereas full length Fn is devoid of motogenic activity. MSF and Fn contain four IGD motifs, located in the 3rd, 5th, 7th and 9th type I modules; these modules are referred to as (3)FnI, (5)FnI, (7)FnI and (9)FnI, respectively. We have previously reported that mutation of IGD motifs in modules (7)FnI and (9)FnI of MSF is sufficient to completely abolish the motogenic response of target adult skin fibroblasts. We now report that the IGD sequences in (3)FnI and (5)FnI are also capable of exhibiting motogenic activity when present within fragments of MSF. When present within (1-5)FnI, these sequences require the presence of serum or vitronectin for their motogenic activity to be manifest, whereas the IGD sequences in (7)FnI and (9)FnI are bioactive in the absence of serum factors. All MSF and IGD-containing peptides stimulated the phosphorylation of the integrin binding protein focal adhesion kinase (FAK) but did not necessarily affect migration. These results suggest that steric hindrance determines the motogenic activity of MSF and Fn, and that both molecules contain cryptic bioactive fragments. (C) 2010 Elsevier Inc. All rights reserved.

    KW - Cell motility

    KW - Fibronectin

    KW - Fibroblasts

    KW - STAPHYLOCOCCUS-AUREUS FNBPA

    KW - GELATIN-BINDING DOMAIN

    KW - TANDEM BETA-ZIPPER

    KW - HUMAN FIBRONECTIN

    KW - FIBROBLAST MIGRATION

    KW - CRYSTAL-STRUCTURES

    KW - CELL MOTILITY

    KW - MATRIX

    KW - ADHESION

    KW - RECEPTOR

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    U2 - 10.1016/j.yexcr.2010.04.003

    DO - 10.1016/j.yexcr.2010.04.003

    M3 - Article

    VL - 316

    SP - 2465

    EP - 2476

    JO - Experimental Cell Research

    JF - Experimental Cell Research

    SN - 0014-4827

    IS - 15

    ER -