title: The LIM-only protein DRAL/FHL2 binds to the cytoplasmic domain of several alpha and beta integrin chains and is recruited to adhesion complexes.
abstract: LIM proteins contain one or more double zinc finger structures (LIM domains) mediating specific contacts between proteins that participate in the formation of multiprotein complexes. We report that the LIM-only protein DRAL/FHL2, with four and a half LIM domains, can associate with alpha(3A), alpha(3B), alpha(7A), and several beta integrin subunits as shown in yeast two-hybrid assays as well as after overexpression in human cells. The amino acid sequence immediately following the conserved membrane-proximal region in the integrin alpha subunits or the C-terminal region with the conserved NXXY motif of the integrin beta subunits are critical for binding DRAL/FHL2. Furthermore, the DRAL/FHL2 associates with itself and with other molecules that bind to the cytoplasmic domain of integrin alpha subunits. Deletion analysis of DRAL/FHL2 revealed that particular LIM domains or LIM domain combinations bind the different proteins. These results, together with the fact that full-length DRAL/FHL2 is found in cell adhesion complexes, suggest that it is an adaptor/docking protein involved in integrin signaling pathways.
authors.affiliation: Institute for Biochemistry II, Medical Faculty, University of Cologne, Joseph-Stelzmann-Strasse 52, 50931 Cologne, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Wixler
authors.forename: D
authors.initials: D
authors.lastname: Geerts
authors.forename: E
authors.initials: E
authors.lastname: Laplantine
authors.forename: D
authors.initials: D
authors.lastname: Westhoff
authors.forename: N
authors.initials: N
authors.lastname: Smyth
authors.forename: M
authors.initials: M
authors.lastname: Aumailley
authors.forename: A
authors.initials: A
authors.lastname: Sonnenberg
authors.forename: M
authors.initials: M
authors.lastname: Paulsson
mesh_terms: D016475:3T3 Cells; D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D002448:Cell Adhesion; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism*; D018398:Homeodomain Proteins; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D060850:LIM-Homeodomain Proteins; D051379:Mice; D009124:Muscle Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D021122:Protein Subunits; D014157:Transcription Factors; D016335:Zinc Fingers
chemical_list: C105987:FHL2 protein, human; C491382:Fhl2 protein, mouse; D018398:Homeodomain Proteins; D016023:Integrins; D060850:LIM-Homeodomain Proteins; D009124:Muscle Proteins; D009363:Neoplasm Proteins; D021122:Protein Subunits; D014157:Transcription Factors