Identification of Protein-tyrosine Phosphatase 1B as the Major Tyrosine Phosphatase Activity Capable of Dephosphorylating and Activating c-Src in Several Human Breast Cancer Cell Lines

Bjorge, Jeffrey D.; Pang, Andrew; Fujita, Daishi

doi:10.1074/jbc.m004852200

Cited by 283 publications

(230 citation statements)

References 60 publications

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“…Pretreatment with PAO, an inhibitor of tyrosine phosphatases, resulted in a marked decrease in basal SRC activity, suggesting that the endogenous tyrosine phosphatases may represent one of the mechanisms that maintain the basal activity of SRC, probably by dephosphorylating Tyr-530 of SRC (10). Indeed, elevated SRC activity in several cancer cell lines correlates with enhanced tyrosine phosphatase activity in these cell lines (26,27), whereas hyperphosphorylation of this residue occurs in cells deficient of tyrosine phosphatase-B, and reduced SRC activity is observed in cells deficient in protein-tyrosine phosphatase-␣ (28, 29). Interestingly, this study showed that specific inhibition of the protein expression of SHP-2 had no effect on the basal activity of SRC in these ECs, suggesting a role for phos- phatases other than SHP-2.…”

Section: Discussionmentioning

confidence: 99%

Activation of SRC Tyrosine Kinases in Response to ICAM-1 Ligation in Pulmonary Microvascular Endothelial Cells

Wang

Pfeiffer

Gaarde

2003

Journal of Biological Chemistry

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Previous studies demonstrated that ICAM-1 ligation on human pulmonary microvascular endothelial cells (ECs) sequentially induces activation of xanthine oxidase and p38 MAPK. Inhibition of these signaling events reduces neutrophil migration to the EC borders. This study examined the role of SRC tyrosine kinases in ICAM-1-initiated signaling within these ECs. Cross-linking ICAM-1 on tumor necrosis factor-␣-pretreated ECs induced an increase in the activity of SRC tyrosine kinases. This increase was inhibited by allopurinol (a xanthine oxidase inhibitor), Me 2 SO (a hydroxyl radical scavenger), or deferoxamine (an iron chelator). Phenylarsine oxide, a tyrosine phosphatase inhibitor, reduced the base-line activity of SRC as well as the increase in SRC activity induced by ICAM-1 cross-linking. Specific inhibition of the protein expression of the SRC homology 2-containing protein-tyrosine phosphatase-2 (SHP-2) by an antisense oligonucleotide prevented the induced SRC activation but had no effect on the basal SRC activity. Activation of SRC tyrosine kinases was accompanied by tyrosine phosphorylation of ezrin at Tyr-146, which was inhibited by PP2, an SRC tyrosine kinase inhibitor. Moreover, PP2 completely inhibited p38 activation, suggesting a role for SRC tyrosine kinases in p38 activation. These data demonstrate that ICAM-1 ligation activates SRC tyrosine kinases and that this activation requires SHP-2 as well as production of reactive oxygen species generated from xanthine oxidase. Activation of SRC tyrosine kinases in turn leads to tyrosine phosphorylation of ezrin, as well as activation of p38, a kinase previously identified to be required for cytoskeletal changes induced by ICAM-1 ligation and for neutrophil migration along the EC surface.Recent studies have provided evidence that ligation of endothelial cell (EC) 1 adhesion molecules including ICAM-1 is capable of initiating outside-in signaling events into ECs upon leukocyte adhesion (reviewed in Refs. 1 and 2). ICAM-1-initiated signaling events into ECs play important roles in modulating neutrophil migration along and/or across endothelium during inflammatory responses. Sans et al. (3) demonstrated that deletion of the ICAM-1 cytoplasmic domain completely inhibits neutrophil transmigration, but not adhesion, in a reconstituted cell line, suggesting a role for ICAM-1-dependent outside-in signaling in mediating neutrophil migration. In addition, inhibition of ICAM-1-inititated signaling events in pulmonary microvascular ECs reduces neutrophil migration along the EC surface to reach EC borders (4).Within the signaling pathways induced through ligation of ICAM-1, activation of SRC tyrosine kinases has been demonstrated in human umbilical vein ECs and rat brain microvascular ECs (5-7). In addition, ligation of ICAM-1 induces activation of LYN, a member of the SRC family tyrosine kinases, in a B cell lymphoma line (8). Each member of the human SRC tyrosine kinase family is composed of a unique region, an SRC homology 2 and 3 domain, a catalytic domain containing r...

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Section: Discussionmentioning

confidence: 99%

Activation of SRC Tyrosine Kinases in Response to ICAM-1 Ligation in Pulmonary Microvascular Endothelial Cells

Wang

Pfeiffer

Gaarde

2003

Journal of Biological Chemistry

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“…PTP1B was also co-immunoprecipitated with b1 integrin and colocalized with integrins at focal adhesions (Arregui et al, 1998). PTP1B has also been purified and identified from breast cancer cells as a phosphatase that could dephosphorylate a peptide containing phosphotyrosine 527 (Bjorge et al, 2000). It has been well described that a third tyrosine phosphatase, Shp2, plays a role in integrin signaling.…”

Section: Dephosphorylation Of Src Y527mentioning

confidence: 99%

The interplay between Src and integrins in normal and tumor biology

2004

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Src family nonreceptor protein tyrosine kinases transduce signals that control normal cellular processes such as cell proliferation, adhesion and motility. Normally, cellular Src is held in an inactive state, but in several cancer types, abnormal events lead to elevated kinase activity of the protein and cause pleiotropic cellular responses inducing transformation and metastasis. A prerequisite of the ability of a cancer cell to undergo metastasis into distant tissues is to penetrate surrounding extracellular matrices. These processes are facilitated by the integrin family of cell adhesion molecules. As is the case with Src, altered integrin activity or substrate affinity can contribute to the neoplastic phenotype. Therefore, understanding the interplay between Src and integrin function has been of intense interest over the past few years. This review focuses on the role of Src and integrin signaling in normal cells and how this is deregulated in human cancer. We will identify the key players in the integrin-mediated signaling pathways involved in cell motility and apoptosis, such as FAK, paxillin and p130 CAS , and discuss how Src signaling affects the formation of focal adhesions and the extracellular matrix.

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“…Interaction with focal adhesion complexes is most likely through interaction with p130 cas and is mediated by a proline rich, SH3-binding domain in PTP1B (Liu et al, 1996). The role of PTP1B in focal adhesion complexes appears to be activation of Src Bjorge et al, 2000) and failure to activate Src leads to impaired integrin-mediated adhesion and signaling . Even though Fig.…”

Section: Maintaining Stable Adhesions: the Nonreceptor Tyrosine Kinasmentioning

confidence: 99%

Turn‐off, drop‐out: Functional state switching of cadherins

Lilien

Balsamo

Arregui

et al. 2002

Developmental Dynamics

149

116

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The classic cadherins are a group of calcium dependent, homophilic cell-cell adhesion molecules that drive morphogenetic rearrangements and maintain the integrity of cell groups through the formation of adherens junctions. The formation and maintenance of cadherin-mediated adhesions is a multistep process and mechanisms have evolved to regulate each step. This suggests that functional state switching plays an important role in development. Among the many challenges ahead is to determine the developmental role that functional state switching plays in tissue morphogenesis and to define the roles of each of the several regulatory interactions that participate in switching. One correlate of the loss of cadherinmediated adhesion, the "turn-off" of cadherin function, is the exit, or "drop-out" of cells from neural and epithelial layers and their conversion to a motile phenotype. We suggest that epithelial mesenchymal conversions may be initiated by signaling pathways that result in the loss of cadherin function. Tyrosine phosphorylation of ␤-catenin is one such mechanism. Enhanced phosphorylation of tyrosine residues on ␤-catenin is almost invariably associated with loss of the cadherin-actin connection concomitant with loss of adhesive function. There are several tyrosine kinases and phosphatases that have been shown to have the potential to alter the phosphorylation state of ␤-catenin and thus the function of cadherins. Our laboratory has focused on the role of the nonreceptor tyrosine phosphatase PTP1B in regulating the phosphorylation of ␤-catenin on tyrosine residues. Our data suggest that PTP1B is crucial for maintenance of N-cadherin-mediated adhesions in embryonic neural retina cells. By using an L-cell model system constitutively expressing N-cadherin, we have worked out many of the molecular interactions essential for this regulatory interaction. Extracellular cues that bias this critical regulatory interaction toward increased phosphorylation of ␤-catenin may be a critical component of many developmental events.

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Identification of Protein-tyrosine Phosphatase 1B as the Major Tyrosine Phosphatase Activity Capable of Dephosphorylating and Activating c-Src in Several Human Breast Cancer Cell Lines

Cited by 283 publications

References 60 publications

Activation of SRC Tyrosine Kinases in Response to ICAM-1 Ligation in Pulmonary Microvascular Endothelial Cells

Activation of SRC Tyrosine Kinases in Response to ICAM-1 Ligation in Pulmonary Microvascular Endothelial Cells

The interplay between Src and integrins in normal and tumor biology

Turn‐off, drop‐out: Functional state switching of cadherins

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