The Roles of Two Distinct Regions of PINCH-1 in the Regulation of Cell Attachment and Spreading
Open Access
- 1 December 2010
- journal article
- Published by American Society for Cell Biology (ASCB) in Molecular Biology of the Cell
- Vol. 21 (23), 4120-4129
- https://doi.org/10.1091/mbc.e10-05-0459
Abstract
Cells attach to the extracellular matrix (ECM) through integrins to form focal adhesion complexes, and this process is followed by the extension of lamellipodia to enable cell spreading. PINCH-1, an adaptor protein essential for the regulation of cell–ECM adhesion, consists of five tandem LIM domains and a small C-terminal region. PINCH-1 is known to interact with integrin-linked kinase (ILK) and Ras suppressor protein 1 (Rsu-1); however, the precise mechanism by which this complex regulates cell–ECM adhesion is not fully understood. We report here that the LIM1 domain of PINCH-1, which associates with ILK to stabilize the expression of this protein, is sufficient for cell attachment but not for cell spreading. In contrast, the C-terminal region of PINCH-1, which binds to Rsu-1, plays a pivotal role in cell spreading but not in cell attachment. We also show that PINCH-1 associates with Rsu-1 to activate Rac1 and that Rac1 activation is necessary for cell spreading. Thus, these data reveal how specific domains of PINCH-1 direct two independent pathways: one utilizing ILK to allow cell attachment, and the other recruiting Rsu-1 to activate Rac1 in order to promote cell spreading.Keywords
This publication has 35 references indexed in Scilit:
- Molecular dissection of the ILK-PINCH-parvin triad reveals a fundamental role for the ILK kinase domain in the late stages of focal-adhesion maturationJournal of Cell Science, 2009
- The structural basis of integrin-linked kinase–PINCH interactionsProceedings of the National Academy of Sciences of the United States of America, 2008
- Talin depletion reveals independence of initial cell spreading from integrin activation and tractionNature, 2008
- The Rsu-1-PINCH1-ILK complex is regulated by Ras activation in tumor cellsEuropean Journal of Cell Biology, 2008
- Regulation of cell‐matrix adhesion dynamics and Rac‐1 by integrin linked kinaseThe FASEB Journal, 2006
- The PINCH–ILK–parvin complexes: assembly, functions and regulationBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2004
- Characterization of PINCH-2, a New Focal Adhesion Protein That Regulates the PINCH-1-ILK Interaction, Cell Spreading, and MigrationJournal of Biological Chemistry, 2002
- Integrin-linked Kinase (ILK) Binding to Paxillin LD1 Motif Regulates ILK Localization to Focal AdhesionsJournal of Biological Chemistry, 2001
- A New LIM Protein Containing an Autoepitope Homologous to "Senescent Cell Antigen"Biochemical and Biophysical Research Communications, 1994
- Integrins: Versatility, modulation, and signaling in cell adhesionCell, 1992