As transmembrane heterodimers, integrins bind to both extracellular ligands and intracellular proteins. We are currently investigating the interaction between integrins and the intracellular protein calreticulin. A prostatic carcinoma cell line (PC-3) was used to demonstrate that calreticulin can be found in the α3 immunoprecipitates of cells plated on collagen type IV, but not when plated on vitronectin. Conversely, αv immunoprecipitates contained calreticulin only when cells were plated on vitronectin, i.e. not when plated on collagen IV. The interactions between these integrins and calreticulin were independent of actin cytoskeleton assembly and were transient, being maximal approx. 10-30 min after the cells came into contact with the substrates prior to complete cell spreading and formation of firm adhesive contacts. We demonstrate that okadaic acid, an inhibitor of intracellular serine/threonine protein phosphatases, inhibited the α3β1-mediated adhesion of PC-3 cells to collagen IV and the α2β1-mediated attachment of Jurkat cells to collagen I. This inhibition by okadaic acid was accompanied by inhibition of the ligand-specific interaction of calreticulin with the respective integrins in the two cell types. Additionally, we found that pharmacological inhibition of mitogen-activated protein kinase kinase (MEK) resulted in prolongation of the calreticulin-integrin interaction, and enhancement of PC-3 cell attachment to collagen IV. We conclude that calreticulin interacts transiently with integrins during cell attachment and spreading. This interaction depends on receptor occupation, is ligand-specific, and can be modulated by protein phosphatase and MEK activity.
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Research Article|
May 10 1999
Ligand-specific, transient interaction between integrins and calreticulin during cell adhesion to extracellular matrix proteins is dependent upon phosphorylation/dephosphorylation events
Marc G. COPPOLINO;
Marc G. COPPOLINO
*Department of Cell Biology, Hospital for Sick Children, 555 University Ave., Toronto, ON, Canada M5G 1X8
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Shoukat DEDHAR
Shoukat DEDHAR
1
†BC Cancer Agency, Jack Bell Research Centre, 2660 Oak St., Vancouver, B. C., Canada V6H 3Z6
1To whom correspondence should be addressed (e-mail sdedhar@interchange.ubc.ca).
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Publisher: Portland Press Ltd
Received:
December 08 1998
Revision Received:
January 27 1999
Accepted:
February 15 1999
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1999
1999
Biochem J (1999) 340 (1): 41–50.
Article history
Received:
December 08 1998
Revision Received:
January 27 1999
Accepted:
February 15 1999
Citation
Marc G. COPPOLINO, Shoukat DEDHAR; Ligand-specific, transient interaction between integrins and calreticulin during cell adhesion to extracellular matrix proteins is dependent upon phosphorylation/dephosphorylation events. Biochem J 15 May 1999; 340 (1): 41–50. doi: https://doi.org/10.1042/bj3400041
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