Cortactin interacts with WIP in regulating Arp2/3 activation and membrane protrusion

Andrew W. Kinley; Scott A. Weed; Alissa M. Weaver; Andrei V. Karginov; Eric Bissonette; John A. Cooper; J. Thomas Parsons

doi:10.1016/S0960-9822(03)00107-6

Cortactin interacts with WIP in regulating Arp2/3 activation and membrane protrusion

Andrew W. Kinley, Scott A. Weed, Alissa M. Weaver, Andrei V. Karginov, Eric Bissonette, John A. Cooper, J. Thomas Parsons

Research output: Contribution to journal › Article › peer-review

150 Scopus citations

Abstract

Background: Modulation of actin cytoskeleton assembly is an integral step in many cellular events. A key regulator of actin polymerization is Arp2/3 complex. Cortactin, an F-actin binding protein that localizes to membrane ruffles, is an activator of Arp2/3 complex. Results: A yeast two-hybrid screen revealed the interaction of the cortactin Src homology 3 (SH3) domain with a peptide fragment derived from a cDNA encoding a region of WASp-Interacting Protein (WIP). GST-cortactin interacted with WIP in an SH3-dependent manner. The subcellular localization of cortactin and WIP coincided at the cell periphery. WIP increased the efficiency of cortactin-mediated Arp2/3 complex activation of actin polymerization in a concentration-dependent manner. Lastly, coexpression of cortactin and WIP stimulated membrane protrusions. Conclusions: WIP, a protein involved in filopodia formation, binds to both actin monomers and cortactin. Thus, recruitment of actin monomers to a cortactin-activated Arp2/3 complex likely leads to the observed increase in cortactin activation of Arp2/3 complex by WIP. These data suggest that a cortactin-WIP complex functions in regulating actin-based structures at the cell periphery.

Original language	English
Pages (from-to)	384-393
Number of pages	10
Journal	Current Biology
Volume	13
Issue number	5
DOIs	https://doi.org/10.1016/S0960-9822(03)00107-6
State	Published - Mar 4 2003

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@article{51beb4119e714542844e0e84e1807e5b,

title = "Cortactin interacts with WIP in regulating Arp2/3 activation and membrane protrusion",

abstract = "Background: Modulation of actin cytoskeleton assembly is an integral step in many cellular events. A key regulator of actin polymerization is Arp2/3 complex. Cortactin, an F-actin binding protein that localizes to membrane ruffles, is an activator of Arp2/3 complex. Results: A yeast two-hybrid screen revealed the interaction of the cortactin Src homology 3 (SH3) domain with a peptide fragment derived from a cDNA encoding a region of WASp-Interacting Protein (WIP). GST-cortactin interacted with WIP in an SH3-dependent manner. The subcellular localization of cortactin and WIP coincided at the cell periphery. WIP increased the efficiency of cortactin-mediated Arp2/3 complex activation of actin polymerization in a concentration-dependent manner. Lastly, coexpression of cortactin and WIP stimulated membrane protrusions. Conclusions: WIP, a protein involved in filopodia formation, binds to both actin monomers and cortactin. Thus, recruitment of actin monomers to a cortactin-activated Arp2/3 complex likely leads to the observed increase in cortactin activation of Arp2/3 complex by WIP. These data suggest that a cortactin-WIP complex functions in regulating actin-based structures at the cell periphery.",

author = "Kinley, {Andrew W.} and Weed, {Scott A.} and Weaver, {Alissa M.} and Karginov, {Andrei V.} and Eric Bissonette and Cooper, {John A.} and Parsons, {J. Thomas}",

note = "Funding Information: We thank Ian G. Macara for the mouse embryonic cDNA library. We thank members of J.T.P.'s laboratory for helpful discussion. This research was supported by National Institutes of Health (NIH)-National Cancer Institute grant CA29243 to J.T.P., NIH/National Institute of Dental and Craniofacial Research grant K22 DE14364 to S.A.W., and NIH grant GM38542 to J.A.C. A.M.W. is a Howard Hughes Medical Institute Physician Postdoctoral Fellow. We thank Julie Head for technical assistance. The assistance of the University of Colorado Cancer Center Tissue Culture and Monoclonal Antibody Core in preparation of the WIP baculovirus is gratefully acknowledged.",

year = "2003",

month = mar,

day = "4",

doi = "10.1016/S0960-9822(03)00107-6",

language = "English",

volume = "13",

pages = "384--393",

journal = "Current Biology",

issn = "0960-9822",

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TY - JOUR

T1 - Cortactin interacts with WIP in regulating Arp2/3 activation and membrane protrusion

AU - Kinley, Andrew W.

AU - Weed, Scott A.

AU - Weaver, Alissa M.

AU - Karginov, Andrei V.

AU - Bissonette, Eric

AU - Cooper, John A.

AU - Parsons, J. Thomas

N1 - Funding Information: We thank Ian G. Macara for the mouse embryonic cDNA library. We thank members of J.T.P.'s laboratory for helpful discussion. This research was supported by National Institutes of Health (NIH)-National Cancer Institute grant CA29243 to J.T.P., NIH/National Institute of Dental and Craniofacial Research grant K22 DE14364 to S.A.W., and NIH grant GM38542 to J.A.C. A.M.W. is a Howard Hughes Medical Institute Physician Postdoctoral Fellow. We thank Julie Head for technical assistance. The assistance of the University of Colorado Cancer Center Tissue Culture and Monoclonal Antibody Core in preparation of the WIP baculovirus is gratefully acknowledged.

PY - 2003/3/4

Y1 - 2003/3/4

N2 - Background: Modulation of actin cytoskeleton assembly is an integral step in many cellular events. A key regulator of actin polymerization is Arp2/3 complex. Cortactin, an F-actin binding protein that localizes to membrane ruffles, is an activator of Arp2/3 complex. Results: A yeast two-hybrid screen revealed the interaction of the cortactin Src homology 3 (SH3) domain with a peptide fragment derived from a cDNA encoding a region of WASp-Interacting Protein (WIP). GST-cortactin interacted with WIP in an SH3-dependent manner. The subcellular localization of cortactin and WIP coincided at the cell periphery. WIP increased the efficiency of cortactin-mediated Arp2/3 complex activation of actin polymerization in a concentration-dependent manner. Lastly, coexpression of cortactin and WIP stimulated membrane protrusions. Conclusions: WIP, a protein involved in filopodia formation, binds to both actin monomers and cortactin. Thus, recruitment of actin monomers to a cortactin-activated Arp2/3 complex likely leads to the observed increase in cortactin activation of Arp2/3 complex by WIP. These data suggest that a cortactin-WIP complex functions in regulating actin-based structures at the cell periphery.

AB - Background: Modulation of actin cytoskeleton assembly is an integral step in many cellular events. A key regulator of actin polymerization is Arp2/3 complex. Cortactin, an F-actin binding protein that localizes to membrane ruffles, is an activator of Arp2/3 complex. Results: A yeast two-hybrid screen revealed the interaction of the cortactin Src homology 3 (SH3) domain with a peptide fragment derived from a cDNA encoding a region of WASp-Interacting Protein (WIP). GST-cortactin interacted with WIP in an SH3-dependent manner. The subcellular localization of cortactin and WIP coincided at the cell periphery. WIP increased the efficiency of cortactin-mediated Arp2/3 complex activation of actin polymerization in a concentration-dependent manner. Lastly, coexpression of cortactin and WIP stimulated membrane protrusions. Conclusions: WIP, a protein involved in filopodia formation, binds to both actin monomers and cortactin. Thus, recruitment of actin monomers to a cortactin-activated Arp2/3 complex likely leads to the observed increase in cortactin activation of Arp2/3 complex by WIP. These data suggest that a cortactin-WIP complex functions in regulating actin-based structures at the cell periphery.

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U2 - 10.1016/S0960-9822(03)00107-6

DO - 10.1016/S0960-9822(03)00107-6

M3 - Article

C2 - 12620186

AN - SCOPUS:0037418592

SN - 0960-9822

VL - 13

SP - 384

EP - 393

JO - Current Biology

JF - Current Biology

IS - 5

ER -

Cortactin interacts with WIP in regulating Arp2/3 activation and membrane protrusion

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