Cortactin is required for integrin-mediated cell spreading

Illés, András; Enyedi, Balázs; Tamás, Péter; Balázs, Annamária; Bőgel, Gábor; Melinda, Melinda; Lukács,; Buday, László

doi:10.1016/j.imlet.2005.11.011

Cited by 13 publications

(11 citation statements)

References 29 publications

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“…Because the SH3-domain of cortactin seemed to be good candidate for SH3PXD2B binding we assessed the binding of the C-terminal-cortactin-GST fusion construct with the W525K substitution. Changing the conserved tryptophan residue to lysine is known to abolish binding to canonical SH3-binding sites in various SH3-domains[39], [40]. As shown in Figure 4C (bottom panel), the GST-cortactin[336–542(W525K)] protein failed to precipitate SH3PXD2B suggesting that their interaction required an intact SH3-domain on cortactin.…”

Section: Resultsmentioning

confidence: 99%

The Homolog of the Five SH3-Domain Protein (HOFI/SH3PXD2B) Regulates Lamellipodia Formation and Cell Spreading

et al. 2011

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Motility of normal and transformed cells within and across tissues requires specialized subcellular structures, e.g. membrane ruffles, lamellipodia and podosomes, which are generated by dynamic rearrangements of the actin cytoskeleton. Because the formation of these sub-cellular structures is complex and relatively poorly understood, we evaluated the role of the adapter protein SH3PXD2B [HOFI, fad49, Tks4], which plays a role in the development of the eye, skeleton and adipose tissue. Surprisingly, we find that SH3PXD2B is requisite for the development of EGF-induced membrane ruffles and lamellipodia, as well as for efficient cellular attachment and spreading of HeLa cells. Furthermore, SH3PXD2B is present in a complex with the non-receptor protein tyrosine kinase Src, phosphorylated by Src, which is consistent with SH3PXD2B accumulating in Src-induced podosomes. Furthermore, SH3PXD2B closely follows the subcellular relocalization of cortactin to Src-induced podosomes, EGF-induced membrane ruffles and lamellipodia. Because SH3PXD2B also forms a complex with the C-terminal region of cortactin, we propose that SH3PXD2B is a scaffold protein that plays a key role in regulating the actin cytoskeleton via Src and cortactin.

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Section: Resultsmentioning

confidence: 99%

The Homolog of the Five SH3-Domain Protein (HOFI/SH3PXD2B) Regulates Lamellipodia Formation and Cell Spreading

et al. 2011

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“…Cortactin exhibits a punctate cytoplasmic staining pattern, but is recruited to E-cadherin-containing adhesion complexes and can be co-immunoprecipitated with E-cadherin from monolayers of MDCK cells (33). It is also a protein that associates with cortical actin and is important for integrin-induced cell spreading (50, 52). An interaction between Syk and cortactin has been described previously in platelets and in K562 chronic myeloid leukemia cells (34, 35).…”

Section: Discussionmentioning

confidence: 99%

Role of the Protein Tyrosine Kinase Syk in Regulating Cell-Cell Adhesion and Motility in Breast Cancer Cells

Zhang

Shrikhande

Alicie

et al. 2009

Molecular Cancer Research

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The expression of the Syk protein tyrosine kinase in breast cancer cells is inversely correlated with invasive growth and metastasis. The expression of Syk inhibits cell motility while supporting the formation of cell clusters by enhancing cell-cell contacts and promoting the redistribution of the adhesion proteins cortactin and vinculin to these contacts. Syk associates physically with cortactin and catalyzes its phosphorylation on tyrosine. The clustering of integrins leads to the phosphorylation of Syk and of numerous cellular proteins in a manner dependent on the activity of the kinase and on the presence of tyrosine 342 located in the linker B region. The ability of Syk to participate in integrin-mediated protein tyrosine phosphorylation correlates well with its ability to inhibit cell motility.

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“…Cortactin knockdown by RNA interference supports its involvement in actin-dependent processes, including specific types of host-pathogen interaction (Selbach and Backert, 2005;Cosen-Binker and Kapus, 2006) and lamellipodium protrusion, although its precise mode of function in the latter process is controversial (Bryce et al, 2005;Kempiak et al, 2005;Illes et al, 2006;van Rossum et al, 2006;Cai et al, 2008), due perhaps to differential efficacy of cortactin down-regulation (Cosen-Binker and Kapus, 2006).…”

Section: Introductionmentioning

confidence: 93%

“…In addition, HS1 has important functions in natural killer cells (Butler et al, 2008). Both cortactin and HS1 are phosphorylated on multiple sites, but the functional subtleties of these phosphorylation events are just beginning to emerge (Martinez-Quiles et al, 2004;Martin et al, 2006;Boyle et al, 2007;Tehrani et al, 2007;Butler et al, 2008;Kruchten et al, 2008).Cortactin knockdown by RNA interference supports its involvement in actin-dependent processes, including specific types of host-pathogen interaction (Selbach and Backert, 2005;Cosen-Binker and Kapus, 2006) and lamellipodium protrusion, although its precise mode of function in the latter process is controversial (Bryce et al, 2005;Kempiak et al, 2005;Illes et al, 2006;van Rossum et al, 2006;Cai et al, 2008), due perhaps to differential efficacy of cortactin down-regulation (Cosen-Binker and Kapus, 2006).To resolve this issue, and to define the precise functions of cortactin in Arp2/3-dependent actin assembly in vivo, we conditionally targeted the murine cortactin gene, and we developed and characterized fibroblast cell lines lacking cortactin. …”

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confidence: 99%

Cortactin Promotes Migration and Platelet-derived Growth Factor-induced Actin Reorganization by Signaling to Rho-GTPases

Lai

Szczodrak

Oelkers

et al. 2009

MBoC

109

112

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Dynamic actin rearrangements are initiated and maintained by actin filament nucleators, including the Arp2/3-complex. This protein assembly is activated in vitro by distinct nucleation-promoting factors such as Wiskott-Aldrich syndrome protein/Scar family proteins or cortactin, but the relative in vivo functions of each of them remain controversial. Here, we report the conditional genetic disruption of murine cortactin, implicated previously in dynamic actin reorganizations driving lamellipodium protrusion and endocytosis. Unexpectedly, cortactin-deficient cells showed little changes in overall cell morphology and growth. Ultrastructural analyses and live-cell imaging studies revealed unimpaired lamellipodial architecture, Rac-induced protrusion, and actin network turnover, although actin assembly rates in the lamellipodium were modestly increased. In contrast, platelet-derived growth factor-induced actin reorganization and Rac activation were impaired in cortactin null cells. In addition, cortactin deficiency caused reduction of Cdc42 activity and defects in random and directed cell migration. Reduced migration of cortactin null cells could be restored, at least in part, by active Rac and Cdc42 variants. Finally, cortactin removal did not affect the efficiency of receptor-mediated endocytosis. Together, we conclude that cortactin is fully dispensable for Arp2/3-complex activation during lamellipodia protrusion or clathrin pit endocytosis. Furthermore, we propose that cortactin promotes cell migration indirectly, through contributing to activation of selected Rho-GTPases. INTRODUCTIONCell migration is a complex process requiring the coordinated activities of multiple cellular machines, driving actin polymerization, actin-myosin II-based force generation, and coupling to the extracellular matrix. However, the relative contribution of each of these machines to the different steps in the motility cycle is just beginning to emerge. Irrespective of the complexity of coordination of these activities, it is commonly agreed that protrusion at the cell front is initiated by localized actin polymerization, to form structures such as lamellipodia or ruffles (Small et al., 2002;Pollard and Borisy, 2003).The best characterized factors driving the nucleation of actin filaments in vertebrate cells are the Arp2/3-complex and formins (Pollard, 2007). Arp2/3-complex activity is considered essential for processes as diverse as lamellipodium protrusion, actin assembly during clathrin-mediated endocytosis, podosome formation, and different types of hostpathogen interaction (Goley and Welch, 2006;Linder, 2007).Activators of Arp2/3-complex are termed nucleation promoting factors (NPFs) and are roughly subdivided into class I and II composed of classical members Wiskott-Aldrich syndrome protein (WASP)/WASP family Verprolin-homologous protein (WAVE) proteins and cortactin, respectively (Welch and Mullins, 2002). This distinction is derived, at least in part, from their mode of interaction with actin: the WH2 domains of class I and tande...

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Cortactin is required for integrin-mediated cell spreading

Cited by 13 publications

References 29 publications

The Homolog of the Five SH3-Domain Protein (HOFI/SH3PXD2B) Regulates Lamellipodia Formation and Cell Spreading

The Homolog of the Five SH3-Domain Protein (HOFI/SH3PXD2B) Regulates Lamellipodia Formation and Cell Spreading

Role of the Protein Tyrosine Kinase Syk in Regulating Cell-Cell Adhesion and Motility in Breast Cancer Cells

Cortactin Promotes Migration and Platelet-derived Growth Factor-induced Actin Reorganization by Signaling to Rho-GTPases

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