Integrin-linked kinase is an adaptor with essential functions during mouse development

Anika Lange, Sara Wickström, Madis Jakobson, Roy Zent, Kirsi Sainio, Reinhard Fässler

    Research output: Contribution to journalArticleScientificpeer-review

    Abstract

    "The development of multicellular organisms requires integrin-mediated interactions between cells and their extracellular environment. Integrin binding to extracellular matrix catalyses assembly of multiprotein complexes, which transduce mechanical and chemical signals that regulate many aspects of cell physiology(1,2). Integrin-linked kinase (Ilk) is a multifunctional protein that binds beta-integrin cytoplasmic domains and regulates actin dynamics by recruiting actin binding regulatory proteins such as alpha-and beta-parvin(3). Ilk has also been shown to possess serine/threonine kinase activity(4) and to phosphorylate signalling proteins such as Akt1 and glycogen synthase kinase 3 beta (Gsk3 beta) in mammalian cells(5); however, these functions have been shown by genetic studies(6,7) not to occur in flies and worms. Here we show that mice carrying point mutations in the proposed autophosphorylation site of the putative kinase domain and in the pleckstrin homology domain are normal. In contrast, mice with point mutations in the conserved lysine residue of the potential ATP-binding site of the kinase domain, which mediates Ilk binding to alpha-parvin, die owing to renal agenesis. Similar renal defects occur in alpha-parvin-null mice. Thus, we provide genetic evidence that the kinase activity of Ilk is dispensable for mammalian development; however, an interaction between Ilk and alpha-parvin is critical for kidney development."
    Original languageEnglish
    JournalNature
    Volume461
    Pages (from-to)1002-1006
    Number of pages5
    ISSN0028-0836
    DOIs
    Publication statusPublished - 2009
    MoE publication typeA1 Journal article-refereed

    Cite this

    Lange, A., Wickström, S., Jakobson, M., Zent, R., Sainio, K., & Fässler, R. (2009). Integrin-linked kinase is an adaptor with essential functions during mouse development. Nature, 461, 1002-1006. https://doi.org/10.1038/nature08468
    Lange, Anika ; Wickström, Sara ; Jakobson, Madis ; Zent, Roy ; Sainio, Kirsi ; Fässler, Reinhard. / Integrin-linked kinase is an adaptor with essential functions during mouse development. In: Nature. 2009 ; Vol. 461. pp. 1002-1006.
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    title = "Integrin-linked kinase is an adaptor with essential functions during mouse development",
    abstract = "{"}The development of multicellular organisms requires integrin-mediated interactions between cells and their extracellular environment. Integrin binding to extracellular matrix catalyses assembly of multiprotein complexes, which transduce mechanical and chemical signals that regulate many aspects of cell physiology(1,2). Integrin-linked kinase (Ilk) is a multifunctional protein that binds beta-integrin cytoplasmic domains and regulates actin dynamics by recruiting actin binding regulatory proteins such as alpha-and beta-parvin(3). Ilk has also been shown to possess serine/threonine kinase activity(4) and to phosphorylate signalling proteins such as Akt1 and glycogen synthase kinase 3 beta (Gsk3 beta) in mammalian cells(5); however, these functions have been shown by genetic studies(6,7) not to occur in flies and worms. Here we show that mice carrying point mutations in the proposed autophosphorylation site of the putative kinase domain and in the pleckstrin homology domain are normal. In contrast, mice with point mutations in the conserved lysine residue of the potential ATP-binding site of the kinase domain, which mediates Ilk binding to alpha-parvin, die owing to renal agenesis. Similar renal defects occur in alpha-parvin-null mice. Thus, we provide genetic evidence that the kinase activity of Ilk is dispensable for mammalian development; however, an interaction between Ilk and alpha-parvin is critical for kidney development.{"}",
    author = "Anika Lange and Sara Wickstr{\"o}m and Madis Jakobson and Roy Zent and Kirsi Sainio and Reinhard F{\"a}ssler",
    year = "2009",
    doi = "10.1038/nature08468",
    language = "English",
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    Lange, A, Wickström, S, Jakobson, M, Zent, R, Sainio, K & Fässler, R 2009, 'Integrin-linked kinase is an adaptor with essential functions during mouse development', Nature, vol. 461, pp. 1002-1006. https://doi.org/10.1038/nature08468

    Integrin-linked kinase is an adaptor with essential functions during mouse development. / Lange, Anika; Wickström, Sara; Jakobson, Madis; Zent, Roy; Sainio, Kirsi; Fässler, Reinhard.

    In: Nature, Vol. 461, 2009, p. 1002-1006.

    Research output: Contribution to journalArticleScientificpeer-review

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    AU - Lange, Anika

    AU - Wickström, Sara

    AU - Jakobson, Madis

    AU - Zent, Roy

    AU - Sainio, Kirsi

    AU - Fässler, Reinhard

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    N2 - "The development of multicellular organisms requires integrin-mediated interactions between cells and their extracellular environment. Integrin binding to extracellular matrix catalyses assembly of multiprotein complexes, which transduce mechanical and chemical signals that regulate many aspects of cell physiology(1,2). Integrin-linked kinase (Ilk) is a multifunctional protein that binds beta-integrin cytoplasmic domains and regulates actin dynamics by recruiting actin binding regulatory proteins such as alpha-and beta-parvin(3). Ilk has also been shown to possess serine/threonine kinase activity(4) and to phosphorylate signalling proteins such as Akt1 and glycogen synthase kinase 3 beta (Gsk3 beta) in mammalian cells(5); however, these functions have been shown by genetic studies(6,7) not to occur in flies and worms. Here we show that mice carrying point mutations in the proposed autophosphorylation site of the putative kinase domain and in the pleckstrin homology domain are normal. In contrast, mice with point mutations in the conserved lysine residue of the potential ATP-binding site of the kinase domain, which mediates Ilk binding to alpha-parvin, die owing to renal agenesis. Similar renal defects occur in alpha-parvin-null mice. Thus, we provide genetic evidence that the kinase activity of Ilk is dispensable for mammalian development; however, an interaction between Ilk and alpha-parvin is critical for kidney development."

    AB - "The development of multicellular organisms requires integrin-mediated interactions between cells and their extracellular environment. Integrin binding to extracellular matrix catalyses assembly of multiprotein complexes, which transduce mechanical and chemical signals that regulate many aspects of cell physiology(1,2). Integrin-linked kinase (Ilk) is a multifunctional protein that binds beta-integrin cytoplasmic domains and regulates actin dynamics by recruiting actin binding regulatory proteins such as alpha-and beta-parvin(3). Ilk has also been shown to possess serine/threonine kinase activity(4) and to phosphorylate signalling proteins such as Akt1 and glycogen synthase kinase 3 beta (Gsk3 beta) in mammalian cells(5); however, these functions have been shown by genetic studies(6,7) not to occur in flies and worms. Here we show that mice carrying point mutations in the proposed autophosphorylation site of the putative kinase domain and in the pleckstrin homology domain are normal. In contrast, mice with point mutations in the conserved lysine residue of the potential ATP-binding site of the kinase domain, which mediates Ilk binding to alpha-parvin, die owing to renal agenesis. Similar renal defects occur in alpha-parvin-null mice. Thus, we provide genetic evidence that the kinase activity of Ilk is dispensable for mammalian development; however, an interaction between Ilk and alpha-parvin is critical for kidney development."

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