The LIM-only protein DRAL/FHL2 binds to the cytoplasmic domain of several alpha and beta integrin chains and is recruited to adhesion complexes.
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.
Wixler
V
V
Institute for Biochemistry II, Medical Faculty, University of Cologne, Joseph-Stelzmann-Strasse 52, 50931 Cologne, Germany.
Geerts
D
D
Laplantine
E
E
Westhoff
D
D
Smyth
N
N
Aumailley
M
M
Sonnenberg
A
A
Paulsson
M
M
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
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