Arg/Abl2 modulates the affinity and stoichiometry of binding of cortactin to F-actin
The Abl family nonreceptor tyrosine kinase Arg/Abl2 interacts with cortactin, an Arp2/3 complex activator, to promote actin-driven cell edge protrusion. Both Arg and cortactin bind directly to filamentous actin (F-actin). While protein-protein interactions between Arg and cortactin have well-characterized downstream effects on the actin cytoskeleton, it is unclear whether and how Arg and cortactin affect each other's actin binding properties. We employ actin cosedimentation assays to show that Arg increases the stoichiometry of binding of cortactin to F-actin at saturation. Using a series of Arg deletion mutants and fragments, we demonstrate that the Arg C-terminal calponin homology domain is necessary and sufficient to increase the stoichiometry of binding of cortactin to F-actin. We also show that interactions between Arg and cortactin are required for optimal affinity between cortactin and the actin filament. Our data suggest a mechanism for Arg-dependent stimulation of binding of cortactin to F-actin, which may facilitate the recruitment of cortactin to sites of local actin network assembly.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2012 |
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| Erschienen: |
2012 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:51 |
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| Enthalten in: |
Biochemistry - 51(2012), 33 vom: 21. Aug., Seite 6644-53 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
MacGrath, Stacey M [VerfasserIn] |
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| Links: |
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| Themen: |
ARG tyrosine kinase |
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| Anmerkungen: |
Date Completed 29.10.2012 Date Revised 21.10.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1021/bi300722t |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM219867887 |
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| 100 | 1 | |a MacGrath, Stacey M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Arg/Abl2 modulates the affinity and stoichiometry of binding of cortactin to F-actin |
| 264 | 1 | |c 2012 | |
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| 500 | |a Date Completed 29.10.2012 | ||
| 500 | |a Date Revised 21.10.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The Abl family nonreceptor tyrosine kinase Arg/Abl2 interacts with cortactin, an Arp2/3 complex activator, to promote actin-driven cell edge protrusion. Both Arg and cortactin bind directly to filamentous actin (F-actin). While protein-protein interactions between Arg and cortactin have well-characterized downstream effects on the actin cytoskeleton, it is unclear whether and how Arg and cortactin affect each other's actin binding properties. We employ actin cosedimentation assays to show that Arg increases the stoichiometry of binding of cortactin to F-actin at saturation. Using a series of Arg deletion mutants and fragments, we demonstrate that the Arg C-terminal calponin homology domain is necessary and sufficient to increase the stoichiometry of binding of cortactin to F-actin. We also show that interactions between Arg and cortactin are required for optimal affinity between cortactin and the actin filament. Our data suggest a mechanism for Arg-dependent stimulation of binding of cortactin to F-actin, which may facilitate the recruitment of cortactin to sites of local actin network assembly | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, P.H.S. | |
| 650 | 7 | |a Actins |2 NLM | |
| 650 | 7 | |a Cortactin |2 NLM | |
| 650 | 7 | |a Cttn protein, mouse |2 NLM | |
| 650 | 7 | |a ARG tyrosine kinase |2 NLM | |
| 650 | 7 | |a EC 2.7.1.- |2 NLM | |
| 650 | 7 | |a Protein-Tyrosine Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.10.1 |2 NLM | |
| 700 | 1 | |a Koleske, Anthony J |e verfasserin |4 aut | |
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