Activation of Arp2/3 complex-mediated actin polymerization by cortactin
- 9 February 2001
- journal article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 3 (3), 259-266
- https://doi.org/10.1038/35060051
Abstract
Cortactin, a filamentous actin (F-actin)-associated protein and prominent substrate of Src, is implicated in progression of breast tumours through gene amplification at chromosome 11q13. However, the function of cortactin remains obscure. Here we show that cortactin co-localizes with the Arp2/3 complex, a de novo actin nucleator, at dynamic particulate structures enriched with actin filaments. Cortactin binds directly to the Arp2/3 complex and activates it to promote nucleation of actin filaments. The interaction of cortactin with the Arp2/3 complex occurs at an amino-terminal domain that is rich in acidic amino acids. Mutations in a conserved amino-acid sequence of DDW abolish both the interaction with the Arp2/3 complex and complex activation. The N-terminal domain is not only essential but also sufficient to target cortactin to actin-enriched patches within cells. Interestingly, the ability of cortactin to activate the Arp2/3 complex depends on an activity for F-actin binding, which is almost 20-fold higher than that of the Arp2/3 complex. Our data indicate a new mechanism for activation of actin polymerization involving an enhanced interaction between the Arp2/3 complex and actin filaments.Keywords
This publication has 40 references indexed in Scilit:
- Tyrosine Phosphorylation of Cortactin Is Required for H2O2-mediated Injury of Human Endothelial CellsPublished by Elsevier BV ,2000
- Tyrosine Phosphorylation of Cortactin Associated with Syk Accompanies Thromboxane Analogue-induced Platelet Shape ChangePublished by Elsevier BV ,1999
- Cell Shrinkage Regulates Src Kinases and Induces Tyrosine Phosphorylation of Cortactin, Independent of the Osmotic Regulation of Na+/H+ ExchangersPublished by Elsevier BV ,1999
- Growth Factor-dependent Phosphorylation of the Actin-binding Protein Cortactin Is Mediated by the Cytoplasmic Tyrosine Kinase FERPublished by Elsevier BV ,1998
- Down-regulation of the Filamentous Actin Cross-linking Activity of Cortactin by Src-mediated Tyrosine PhosphorylationPublished by Elsevier BV ,1997
- Physical and Functional Association of Cortactin with Syk in Human Leukemic Cell Line K562Journal of Biological Chemistry, 1996
- Mechanical Strain Induces pp60 Activation and Translocation to Cytoskeleton in Fetal Rat Lung CellsPublished by Elsevier BV ,1996
- The involvement of the chromosome 11q13 region in human malignancies: Cyclin D1 and EMS1 are two new candidate oncogenes-a reviewGene, 1995
- The product of the EMS1 gene, amplified and overexpressed in human carcinomas, is homologous to a v-src substrate and is located in cell-substratum contact sites.Molecular and Cellular Biology, 1993
- Identification and characterization of a novel cytoskeleton-associated pp60src substrate.Molecular and Cellular Biology, 1991