ER-bound PTP1B is targeted to newly forming cell-matrix adhesions
Open Access
- 1 April 2006
- journal article
- Published by The Company of Biologists in Journal of Cell Science
- Vol. 119 (7), 1233-1243
- https://doi.org/10.1242/jcs.02846
Abstract
Here, we define the mechanism through which protein tyrosine phosphatase 1B (PTP1B) is targeted to cell-matrix adhesion sites. Green fluorescent protein (GFP)-labeled PTP1B bearing the substrate-trapping mutation D181A was found in punctate structures in lamellae. The puncta co-localized with focal adhesion kinase (FAK) and Src, and defined the distal tips of cell-matrix adhesion sites identified with paxillin and vinculin. PTP1B is largely associated with the external face of the endoplasmic reticulum (ER) and the puncta develop from ER projections over cell-matrix adhesion sites, a process dependent on microtubules. Deletion of the ER-targeting sequence resulted in cytosolic localization and altered the distribution of PTP1B at cell-matrix foci, whereas mutations disrupting interactions with Src homology 3 (SH3) domains, and the insulin and cadherin receptors had no effect. PTP1B recognizes substrates within forming adhesion foci as revealed by its preferential association with paxillin as opposed to zyxin-containing foci. Our results suggest that PTP1B targets to immature cell-matrix foci in newly forming lamellae by dynamic extensions of the ER and contributes to the maturation of these sites.Keywords
This publication has 60 references indexed in Scilit:
- The Role of Protein-tyrosine Phosphatase 1B in Integrin SignalingPublished by Elsevier ,2005
- Focal adhesion kinase: in command and control of cell motilityNature Reviews Molecular Cell Biology, 2005
- FAK–Src signalling through paxillin, ERK and MLCK regulates adhesion disassemblyNature Cell Biology, 2004
- Protein-tyrosine Phosphatase 1B Mediates the Effects of Insulin on the Actin Cytoskeleton in Immortalized FibroblastsJournal of Biological Chemistry, 2003
- Phosphatases in cell–matrix adhesion and migrationNature Reviews Molecular Cell Biology, 2003
- Coupling membrane protrusion and cell adhesionJournal of Cell Science, 2003
- Attenuation of Adhesion-dependent Signaling and Cell Spreading in Transformed Fibroblasts Lacking Protein Tyrosine Phosphatase-1BJournal of Biological Chemistry, 2001
- PTP1B regulates neurite extension mediated by cell-cell and cell-matrix adhesion moleculesJournal of Neuroscience Research, 2001
- Src family kinases are required for integrin but not PDGFR signal transductionThe EMBO Journal, 1999
- c-Src enhances the spreading of src-/- fibroblasts on fibronectin by a kinase-independent mechanism.Genes & Development, 1995