Cited by 254Cellular Mechanics and InteractionsAxon Guidance and Neuronal SignalingProtein Kinase Regulation and GTPase Signaling

Identification of a Novel Cortactin SH3 Domain-Binding Protein and Its Localization to Growth Cones of Cultured Neurons

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Du, Yunrui, Weed, Scott A., Xiong, Wen-Cheng, Marshall, Trudy D., Parsons, J. Thomas·1998·Molecular and Cellular Biology

Abstract

Cortactin is an actin-binding protein that contains several potential signaling motifs including a Src homology 3 (SH3) domain at the distal C terminus. Translocation of cortactin to specific cortical actin structures and hyperphosphorylation of cortactin on tyrosine have been associated with the cortical cytoskeleton reorganization induced by a variety of cellular stimuli. The function of cortactin in these processes is largely unknown in part due to the lack of information about cellular binding partners for cortactin. Here we report the identification of a novel cortactin-binding protein of approximately 180 kDa by yeast two-hybrid interaction screening. The interaction of cortactin with this 180-kDa protein was confirmed by both in vitro and in vivo methods, and the SH3 domain of cortactin was found to direct this interaction. Since this protein represents the first reported natural ligand for the cortactin SH3 domain, we designated it CortBP1 for cortactin-binding protein 1. CortBP1 contains two recognizable sequence motifs within its C-terminal region, including a consensus sequence for cortactin SH3 domain-binding peptides and a sterile alpha motif. Northern and Western blot analysis indicated that CortBP1 is expressed predominately in brain tissue. Immunofluorescence studies revealed colocalization of CortBP1 with cortactin and cortical actin filaments in lamellipodia and membrane ruffles in fibroblasts expressing CortBP1. Colocalization of endogenous CortBP1 and cortactin was also observed in growth cones of developing hippocampal neurons, implicating CortBP1 and cortactin in cytoskeleton reorganization during neurite outgrowth.

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Authors
Du, Y., Weed, S. A., Xiong, W.-C., Marshall, T. D., & Parsons, J. T.
Affiliations
University of Virginia (US)
Corresponding author
Parsons, J. Thomas
Venue
Molecular and Cellular Biology
Published
1998-10-01
Volume
18
Issue
10
Pages
5838-5851
ISSN
  • 0270-7306 (ISSN-L)
  • 1098-5549
OpenAlex
W1832262637
Cited by
254
References
83
Citations by year
2026: 1 · 2025: 2 · 2024: 3 · 2023: 5 · 2022: 10 · 2021: 6 · 2020: 12 · 2019: 5 · 2018: 10 · 2017: 4 · 2016: 7 · 2015: 12 · 2014: 10 · 2013: 6 · 2012: 8
FWCI
3.96
Type
journal article
Language
en
Open access
Locations
  • Molecular and Cellular Biology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Health and Human Services
  • National Institutes of Health (CA29243)
  • National Cancer Institute (CA40042, R37CA029243, CA 29243, R01CA029243, F32 CA75695-01, P01CA040042, F32CA075695)
  • National Institute of Neurological Disorders and Stroke (F32NS009918)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
cortactin, SH3 domain, actin cytoskeleton remodeling, growth cones, hippocampal neurons, neurite outgrowth, lamellipodia, ruffles, sterile alpha motif, protein-protein interaction
MeSH terms
Amino Acid Sequence, Animals, Base Sequence, Carrier Proteins, Cell Differentiation, Cells, Cultured, Cloning, Molecular, Fibroblasts, Hippocampus, Male, Microfilament Proteins, Molecular Sequence Data, Nerve Tissue Proteins, Neurons, Proteins, Rabbits, Subcellular Fractions, Tissue Distribution, 3T3 Cells, Rats, Sprague-Dawley, DNA, Complementary, src Homology Domains, Growth Cones, Adaptor Proteins, Signal Transducing, Cortactin, Mice, Rats

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