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  • The EMBO Journal (2003) 22, 1014 - 1024
  • doi:10.1093/emboj/cdg101

Attenuation of cell adhesion in lymphocytes is regulated by CYTIP, a protein which mediates signal complex sequestration

Thomas Boehm1,6, Susanne Hofer2,6, Patricia Winklehner2, Bettina Kellersch1, Christiane Geiger1, Alexander Trockenbacher3, Susanne Neyer2, Heidi Fiegl2, Susanne Ebner2, Lennart Ivarsson2, Rainer Schneider3, Elisabeth Kremmer4, Christine Heufler2 and Waldemar Kolanus1,5

  1. Laboratory for Molecular Biology, Gene Center, University of Munich, Feodor-Lynen-Stras zlige 25, D-81377 Munich, Germany
  2. Department of Dermatology, University of Innsbruck, Anichstras zlige 35, A-6020 Innsbruck, Austria
  3. Institute of Biochemistry, University of Innsbruck, Peter Mayerstras zlige 1, Innsbruck, Austria
  4. GSF-National Research Center for Environment and Health, Marchioninistras zlige 25, D-81377 Munich, Germany
  5. Present address: Institute of Molecular Physiology and Developmental Biology, Division of Cellular Biochemistry, University of Bonn, Karlrobert-Kreiten Stras zlige 13, D-53115 Bonn, Germany
  6. T.Boehm and S.Hofer contributed equally to this work

Correspondence to:

Christine Heufler, E-mail: christine.heufler@uibk.ac.at

Waldemar Kolanus, E-mail: wkolanus@uni-bonn.de

Received 22 April 2002; Accepted 9 January 2003; Revised 20 December 2002

An important theme in molecular cell biology is the regulation of protein recruitment to the plasma membrane. Fundamental biological processes such as proliferation, differentiation or leukocyte functions are initiated and controlled through the reversible binding of signaling proteins to phosphorylated membrane components. This is mediated by specialized interaction modules, such as SH2 and PH domains. Cytohesin-1 is an intracellular guanine nucleotide exchange factor, which regulates leukocyte adhesion. The activity of cytohesin-1 is controlled by phospho inositide-dependent membrane recruitment. An interacting protein was identified, the expression of which is upregulated by cytokines in hematopoietic cells. This molecule, CYTIP, is also recruited to the cell cortex by integrin signaling via its PDZ domain. However, stimulation of Jurkat cells with phorbol ester results in re-localization of CYTIP to the cytoplasm, and membrane detachment of cytohesin-1 strictly requires co-expression of CYTIP. Con sequently, stimulated adhesion of Jurkat cells to intracellular adhesion molecule-1 is repressed by CYTIP. These findings outline a novel mechanism of signal chain abrogation through sequestration of a limiting component by specific protein–protein interactions.

  • Keywords:

    • cell adhesion,
    • CYTIP,
    • cytohesin-1,
    • integrins,
    • lymphocytes