Our main research interest is the regulation and function of the collagen receptor integrins, a1b1 and a2b1. One of our contribution to integrin research has been the observation, that a2b1 integrin plays an important role in the regulation of matrix metalloproteinase expression and in cell invasion. We were also the first ones who found out the in vivo role of the another main collagen receptor, a1b1 integrin, that seems to be a feed-back regulator of collagen gene expression. We have also described specific signaling pathways regulated by the interaction of a2b1 integrin with three dimensional collagenous matrix. We will continue this research project to find out the exact molecular mechanism of collagen receptor signaling. Six years ago we started a project analyzing the structure-function relationship of a1b1 and a2b1 integrins in order to unveil the structural bases of collagen recognition and to design specific molecules blocking integrin function. This project is a collaboration with Professor Mark Johnson's group (Åbo Akademi University). The Integrin research group is working in two different laboratories: MediCity Research Laboratory in the University of Turku and Cell Biology Department in the University of Jyväskylä. Dr. Jyrki Heino is currently the professor of cell biology in the University of Jyväskylä. In addition 4 PhDs, 8 graduate students (MSc or MD) and two technicians are working in the project.

See also http://www.jyu.fi/~jakapyla/

• Structure-function analysis of the collagen receptor integrins
• Integrin signaling
• Integrin in cancer invasion
• Integrin internalization and intracellular transport
• Integrins as picornavirus receptors

• T. Riikonen, L. Koivisto, P. Vihinen, and J. Heino. Transforming growth factor-b induces collagen gel constraction by increasing the expression of a2b1 integrin in osteogenic cells. J Biol Chem 270: 376-382, 1995.
  
  PubMed - abstract

• T. Riikonen, J. Westermarck, L. Koivisto, A. Broberg,V.-M. Kähäri, and J. Heino. a2b1 integrin is a positive regulator of collagenase (MMP-1) and collagen a1(I) gene expression . J Biol Chem 270: 13548-13552, 1995.
  
  PubMed - abstract

• P. Huttunen, J. Heino, and T. Hyypiä. Echovirus-1 replication, but not virus binding to its receptor, VLA-2, is required for the activation of cellular immediate early genes. J Virol 71: 4176-4180, 1997.
  
  PubMed - abstract

• J. Ivaska, J. Käpylä, O. Pentikäinen, A.M. Hoffren, J. Hermonen, P. Huttunen, M. Johnson, and J. Heino. A peptide inhibiting the collagen binding function of integrin a2I domain. J Biol Chem 274: 3513-3521, 1999.
  
  PubMed - abstract

• L. Ravanti, J. Heino, C. López-Otín, and V.M. Kähäri. Collagenase-3 (MMP-13) expression by dermal fibroblasts is dependent on contact to three-dimensional collagen and requires activity of p38 stress-activated protein kinase. J Biol Chem 274: 2446-2455, 1999.
  
  PubMed - abstract

• H. Gardner, A. Broberg, A. Pozzi, M. Laato, and J. Heino. Absence of integrin a1b1 in the mouse causes loss of feedback regulation of collagen synthesis in normal and wounded dermis. J Cell Sci 112: 263-272, 1999.
  
  PubMed - abstract

• O. Pentikäinen, A.-M. Hoffrén, J. Ivaska, J. Käpylä, T. Nyrönen, J. Heino, and M. Johnson. RKKH peptides from the snake venom metalloproteinase of Bothrops jararaca bind near the MIDAS site of the human integrin a2I-domain. J Biol Chem 274: 31493-31505, 1999.
  
  PubMed - abstract

• J. Ivaska, H. Reunanen, J. Westermarck, V-M. Kähäri, and J. Heino. Integrin a2b1 mediates isoform specific activation of p38 and upregulation of collagen gene transcription by a mechanism involving the a2 cytoplasmic tail. J Cell Biol 147: 401-416, 1999.
  
  PubMed - abstract

• J. Käpylä, J. Ivaska, R. Riikonen, P. Nykvist, O. Pentikäinen, M. Johnson, and J. Heino. Integrin a2I domain recognizes type I and type IV collagens by different mechanisms. J Biol Chem. 275: 3348-3354, 2000.
  
  PubMed - abstract

• P. Nykvist, H. Tu, J. Ivaska, J. Käpylä, T. Pihlajaniemi, and J. Heino. Distinct recognition of collagen subtypes by a1b1 and a2b1 integrins - a1b1 in the cellular receptor of type XIII collagen. J Biol Chem 275: 8255-8261, 2000
  
  PubMed - abstract

  

Doctoral Theses

• Regulation and function of collagen receptor integrins in osteosarcoma cells. Pia Vihinen, 1996.

• Cell adhesion receptors in rheumatoid synovial lining. Laura Pirilä, 1997

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• Integrin-type collagen receptors as regulators of cell behaviour and gene expression. Terhi Lehtinen, 1998.

• Thesis: Molecular pathogenesis of echovirus-1 infection. Pasi Huttunen, 1999.

• Cellular collagen receptors: Different ligand recognition and signal transduction functions. Johanna Ivaska, 2000.