RasGAP-like Protein IQGAP1 is Expressed by Human Keratinocytes and Recognized by Autoantibodies in Association with Bullous Skin Disease

Stefan Presslauer, Gabriele Hinterhuber, Karla Cauza, Klaus Wolff, Dagmar Foedinger, Reinhard Horvat, Klemens Rappersberger
2003 Journal of Investigative Dermatology  
Autoantibodies in patients with autoimmune bullous skin diseases, such as pemphigus or bullous pemphigoid are of diagnostic value and might play a part in the pathogenic scenario. In this study we present ¢ve patients with erythematous plaques, subepidermal blister formation of the skin, and the presence of circulating autoantibodies directed against a so far unrecognized 190 kDa antigen in human keratinocytes. Amino acid sequence analysis identi¢ed the protein as IQGAP1, a recently described
more » ... man Ras GTPase-activating-like protein suspected to act as an e¡ector molecule for Cdc42 and Rac1, members of the Rho small GTPase family and to play a key part in regulating E-cadherinmediated cell adhesion. The protein is selectively recognized by a monoclonal anti-IQGAP1 antibody on western blots and immunoprecipitates from keratinocyte extracts. Indirect immuno£uorescence locates IQ-GAP1 within individual keratinocytes in a cytoplasmic pattern and along the cell periphery at adhesive sites. Our results demonstrate IQGAP1, a newly described multifunctional protein, to be constitutively expressed in human keratinocytes where it may contribute to the integrity of the epidermal layer. Furthermore, we found autoantibodies reacting with IQGAP1 in patients with bullous skin eruptions most apparently belonging to the spectrum of bullous pemphigoid.
doi:10.1046/j.1523-1747.2003.12070.x pmid:12603848 fatcat:f3nn7kntirhlfje27kzluwbfyq