Regulation of tensin-promoted cell migration by its focal adhesion binding and Src homology domain 2

Chen, Huaiyang; Lo, Su Hao

doi:10.1042/bj20021308

Cited by 54 publications

(53 citation statements)

References 34 publications

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“…Our data therefore strongly suggest that tensin binding has a RhoGAPindependent role that contributes to the biological activity of DLC. Our biochemical analyses provide a potential alternate mechanism because we observe that DLC1 can compete with ␤3-integrin for binding the PTB domain and with several proteins for binding the SH2 domain; a previous mutant analysis of tensin1 reported that both of these tensin domains are required for tensin-dependent migration (24). Thus, DLC1, and presumably the other DLC family members, is a multifunctional protein whose tensin binding and RhoGAP activities do not depend on each other, but both activities are required for biological activity.…”

Section: Discussionmentioning

confidence: 99%

“…The tensin PTB domain binds the intracellular portion of several ␤-integrins, including ␤3-integrin (26), and is required for tensin-dependent cell migration (24). Given that DLC1 binds the tensin PTB domain, we speculated that DLC1 might compete with ␤3-integrin for binding and that similar sequences in the PTB domain might be required for binding each protein.…”

Section: Dlc1 Competes With ␤3-integrin For Binding To the Tensin Ptbmentioning

confidence: 99%

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Oncogenic inhibition by a deleted in liver cancer gene requires cooperation between tensin binding and Rho-specific GTPase-activating protein activities

Qian¹,

Li²,

Asmussen³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

184

243

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The three deleted in liver cancer genes (DLC1-3) encode RhoGTPase-activating proteins (RhoGAPs) whose expression is frequently down-regulated or silenced in a variety of human malignancies. The RhoGAP activity is required for full DLC-dependent tumor suppressor activity. Here we report that DLC1 and DLC3 bind to human tensin1 and its chicken homolog. The binding has been mapped to the tensin Src homology 2 (SH2) and phosphotyrosine binding (PTB) domains at the C terminus of tensin proteins. Distinct DLC1 sequences are required for SH2 and PTB binding. DCL binding to both domains is constitutive under basal conditions. The SH2 binding depends on a tyrosine in DCL1 (Y442) but is phosphotyrosine-independent, a highly unusual feature for SH2 binding. DLC1 competed with the binding of other proteins to the tensin C terminus, including ␤3-integrin binding to the PTB domain. Point mutation of a critical tyrosine residue (Y442F) in DLC1 rendered the protein deficient for binding the tensin SH2 domain and binding full-length tensin. The Y442F protein was diffusely cytoplasmic, in contrast to the localization of wild-type DLC1 to focal adhesions, but it retained the ability to reduce the intracellular levels of Rho-GTP. The Y442F mutant displayed markedly reduced biological activity, as did a mutant that was RhoGAP-deficient. The results suggest that DLC1 is a multifunctional protein whose biological activity depends on cooperation between its tensin binding and RhoGAP activities, although neither activity depends on the other. DLC1 ͉ Src homology 2 and phosphotyrosine binding domains ͉ tumor suppressor gene

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Section: Discussionmentioning

confidence: 99%

Section: Dlc1 Competes With ␤3-integrin For Binding To the Tensin Ptbmentioning

confidence: 99%

Oncogenic inhibition by a deleted in liver cancer gene requires cooperation between tensin binding and Rho-specific GTPase-activating protein activities

Qian¹,

Li²,

Asmussen³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

184

243

View full text Add to dashboard Cite

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“…3) Low levels of FGFR1 are expressed, and the cells are efficiently stimulated by bFGF (37); thus, the specific effects of VHL knock-down on FGFR signaling can be observed unambiguously. 4) HEK293 cells possess a moderate capacity of chemotactic migration toward serum (38). Also, we expressed either wild type HIF-2␣ (HIF-2␣ (WT)) or a constitutively active HIF-2␣ (HIF-2␣ (P/A)) in order to delineate HIF-dependent and -independent roles of VHL.…”

Section: Fgfr1 and Erk Activities Regulate Cell Migration In Vhl Mutantmentioning

confidence: 99%

Endocytic Function of von Hippel-Lindau Tumor Suppressor Protein Regulates Surface Localization of Fibroblast Growth Factor Receptor 1 and Cell Motility

Hsu

Adereth

Kose

et al. 2006

Journal of Biological Chemistry

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The tumor suppressor VHL (von Hippel-Lindau protein) serves as a negative regulator of hypoxia-inducible factor-␣ subunits. However, accumulated evidence indicates that VHL may play additional roles in other cellular functions. We report here a novel hypoxia-inducible factor-independent function of VHL in cell motility control via regulation of fibroblast growth factor receptor 1 (FGFR1) endocytosis. In VHL null tumor cells or VHL knock-down cells, FGFR1 internalization is defective, leading to surface accumulation and abnormal activation of FGFR1. The enhanced FGFR1 activity directly correlates with increased cell migration. VHL disease mutants, in two of the mutation hot spots favoring development of renal cell carcinoma, failed to rescue the above phenotype. Interestingly, surface accumulation of the chemotactic receptor appears to be selective in VHL mutant cells, since other surface proteins such as epidermal growth factor receptor, platelet-derived growth factor receptor, IGFR1, and c-Met are not affected. We demonstrate that 1) FGFR1 endocytosis is defective in the VHL mutant and is rescued by reexpression of wild-type VHL, 2) VHL is recruited to FGFR1-containing, but not EGFR-containing, endosomal vesicles, 3) VHL exhibits a functional relationship with Rab5a and dynamin 2 in FGFR1 internalization, and 4) the endocytic function of VHL is mediated through the metastasis suppressor Nm23, a protein known to regulate dynamin-dependent endocytosis.The von Hippel-Lindau disease is an inherited disorder that manifests in tumor formation in multiple organs (1, 2). The disease is characterized by highly vascularized tumors mainly due to overproduction of angiogenic factors. The underlying genetic defect was identified as mutations in the VHL tumor suppressor gene (3). The biological role of VHL is prominently linked to its E3 3 ubiquitin ligase activity toward a subset of cellular proteins, thus promoting their ubiquitination and degradation (4, 5). Prominent among its cellular targets are the ␣ subunits (1␣, 2␣, and 3␣) of the key transcription factor, hypoxia-inducible factor (HIF), involved in the cellular oxygen-sensing mechanism (6 -8).Tumorigenic mutations that affect E3 ligase function of VHL result in constitutive stabilization of HIF-␣, leading to transcriptional activation of several target genes of HIF (9), including those encoding critical angiogenic factors such as vascular endothelial growth factor and enzymes involved in glucose metabolism (10). Renal cell carcinomas (RCCs) harboring VHL mutations are often metastatic, and reexpression of wild-type VHL suppresses the metastatic behavior in RCC-derived cell lines (11,12), although the mechanisms remain unclear. VHL mutant cells exhibit increased scattering upon hepatocyte growth factor treatment (13). Enhanced response to SDF-1 (stromal cell-derived factor-1), due to overexpression of chemokine receptor CXCR4, was also recently identified as a possible mechanism by which VHL tumors might disseminate to distant organs (14). On the other hand, accumul...

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“…Tensin is particularly interesting in the myriad of focal adhesion proteins because it can bind to actin microfilaments at multiple sites (Lo et al 1994b), enabling tensin both to cap the growing ends of actin filaments and to crosslink actin filaments (Lo et al 1994b;Chuang et al 1995). In addition, tensin is phosphorylated on tyrosine residues (Salgia et al 1995) and contains an SH2 domain (Davis et al 1991), suggesting that tensin might participate in signal transduction cascades relevant to various cellular functions, including cell migration (Chen et al 2002;Chen and Lo 2003), differentiation (Hiura et al 1995), regeneration (Ishii and Lo 2001), and apoptosis (Kook et al 2003). Several factors, including the ECM, platelet-derived growth factor, thrombin, angiotensin, and oncogenes, induce tensin-mediated signal transduction (Chen et al 2002).…”

Section: Discussionmentioning

confidence: 99%

Tensin Is Expressed in Glomerular Mesangial Cells and Is Related to Their Attachment to Surrounding Extracellular Matrix

Takahara

Shirato

Asanuma

et al. 2004

J Histochem Cytochem.

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S U M M A R Y Glomerular expression of tensin was immunohistochemically studied in normal and diseased rat kidneys to determine whether tensin might be related to specific binding in individual glomerular cells. Normal rat kidneys displayed an intense immunofluorescence reaction for tensin along the basal aspects of proximal and distal tubule cells and parietal epithelial cells of Bowman's capsules. In glomeruli, a positive reaction for tensin was detected only in the mesangial areas. Immunoelectron microscopy revealed a positive reaction in the mesangial cell (MC) processes. RT-PCR and immunoprecipitation demonstrated mRNA and protein levels of tensin in cultured rat MCs. Mesangial tensin expression was decreased when the mesangium was injured by Habu snake venom. During the regenerative process after mesangiolysis, tensin expression was not detected in early-phase proliferating MCs that did not have extracellular matrix (ECM). The expression of tensin recovered in late-phase proliferating MCs, which became attached to regenerated ECM. It appears that tensin is related to MC attachment to surrounding ECM, which suggests that signal transduction regulated by tensin may be related to a specific mechanism of MC matrix regeneration. Furthermore, tensin can act as a marker for rat MCs because the expression of tensin was detected only in MCs in glomeruli.

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Regulation of tensin-promoted cell migration by its focal adhesion binding and Src homology domain 2

Cited by 54 publications

References 34 publications

Oncogenic inhibition by a deleted in liver cancer gene requires cooperation between tensin binding and Rho-specific GTPase-activating protein activities

Oncogenic inhibition by a deleted in liver cancer gene requires cooperation between tensin binding and Rho-specific GTPase-activating protein activities

Endocytic Function of von Hippel-Lindau Tumor Suppressor Protein Regulates Surface Localization of Fibroblast Growth Factor Receptor 1 and Cell Motility

Tensin Is Expressed in Glomerular Mesangial Cells and Is Related to Their Attachment to Surrounding Extracellular Matrix

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