Inducible phosphorylation of cortactin is not necessary for cortactin-mediated actin polymerisation

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

doi:10.1016/j.cellsig.2005.07.012

Cited by 11 publications

(10 citation statements)

References 32 publications

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“…cDNAs corresponding to the N-terminal part (amino acids 1–334) and C-terminal part (amino acids 336–542) of cortactin were also amplified by PCR and subcloned into EcoRI/XhoI sites of pGEX-4T-1 plasmid. The Src construct was a generous gift of Julian Downward (Cancer Research UK, London) and was used earlier [55].…”

Section: Methodsmentioning

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: Methodsmentioning

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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“…Although previous studies have found that introduction of a cortactin mutant deficient in tyrosine phosphorylation impairs cell motility, tumor invasion, invadopodia, and podosome formation (30 -33), no solid evidence for a role of phosphorylated cortactin in actin polymerization either in cells (34) or in vitro 4 has been found. Therefore, the physiological role of cortactin tyrosine phosphorylation remains unknown.…”

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confidence: 87%

Receptor-mediated Endocytosis Involves Tyrosine Phosphorylation of Cortactin

Zhu

Zeng

et al. 2007

Journal of Biological Chemistry

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Efficient internalization of cell surface receptors requires actin polymerization mediated by Arp2/3 complex and cortactin, a prominent substrate of the protein-tyrosine kinase Src. However, the significance of cortactin tyrosine phosphorylation in endocytosis is unknown. We found that overexpression of a cortactin mutant deficient in tyrosine phosphorylation decreased transferrin uptake. Suppression of cortactin expression by RNA interference also reduced transferrin internalization. Such inhibition was effectively rescued by overexpressing wild-type cortactin but not a cortactin mutant deficient in tyrosine phosphorylation or a mutant with deletion of the Src homology 3 domain. Likewise, purified phosphorylation-null cortactin failed to restore the formation of clathrin-coated vesicles in a cortactin-depleted cell extract. In vitro analysis revealed that Src-mediated phosphorylation enhanced the association of cortactin with dynamin-2 in a tyrosine phosphorylation-dependent manner. Quantitative analysis demonstrated that Src enhances the affinity of cortactin for dynamin-2 by more than 3-fold. On the other hand, Src-treated dynamin-2 had no effect on its interaction with cortactin. These data indicate that Src kinase is implicated in clathrin-mediated endocytosis by phosphorylation of cortactin.

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“…The SH3 domain may enhance actin nucleation via binding to the WASP, WIP, and dynamin 2 [ 46 ]. Once the Arp2/3 is activated, it will bind to a pre-existing actin filament and then produce a new filament, which with a 70° branch [ 47 ]. When the structure is formed, cortactin stabilizes branched actin networks.…”

Section: Cortactin Interacts With Actin Cytoskeletonmentioning

confidence: 99%

“…Cortactin interacts with numerous binding partners [ 24 ], and is activated by several post-translational modifications. Cortactin was initially characterized via its tyrosine phosphorylation activity, in v-Src transformed cells [ 1 , 47 ]. Src kinase phosphorylates cortactin at three tyrosine residues, include Y421, Y466, and Y482 [ 17 , 47 ].…”

Section: Cortactin Promotes Cell Migrationmentioning

confidence: 99%

“…Cortactin was initially characterized via its tyrosine phosphorylation activity, in v-Src transformed cells [ 1 , 47 ]. Src kinase phosphorylates cortactin at three tyrosine residues, include Y421, Y466, and Y482 [ 17 , 47 ]. Tyrosine phosphorylation occurs primarily at Y421 and Y466, the two sites are localized within the proline-rich domain [ 70 , 71 ].…”

Section: Cortactin Promotes Cell Migrationmentioning

confidence: 99%

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Cortactin in cancer cell migration and invasion

Yin

2017

Oncotarget

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Cortactin, a substrate of sarcoma (Src) kinases, is an actin-binding protein that is involved in cytoskeletal regulation, and is frequently overexpressed in cancer cells. Binding to the actin related protein 2/3 (Arp2/3) complex stimulates cortactin activity, which promotes F-actin nucleation and assembly. Cortactin promotes cancer cell migration and invasion, and plays a pivotal role in invadopodia formation and extra cellular matrix degradation. Overexpression of cortactin, by amplification of the chromosomal band 11q13, increases tumor aggressiveness. In this review, we report on the current knowledge and potential mechanisms of action of cortactin as a critical mediator of cancer cell migration and invasion.

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Inducible phosphorylation of cortactin is not necessary for cortactin-mediated actin polymerisation

Cited by 11 publications

References 32 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

Receptor-mediated Endocytosis Involves Tyrosine Phosphorylation of Cortactin

Cortactin in cancer cell migration and invasion

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