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Molecular and Cellular Biology, October 1998, p. 5838-5851, Vol. 18, No. 10
Department of Microbiology and Cancer Center,
University of Virginia Health Science Center, Charlottesville,
Virginia 22908
Received 23 April 1998/Returned for modification 21 May
1998/Accepted 18 June 1998
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.
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Identification of a Novel Cortactin SH3 Domain-Binding Protein
and Its Localization to Growth Cones of Cultured Neurons
and
*
Corresponding author. Mailing address: Department of
Microbiology, Box 441, Health Science Center, University of Virginia, Charlottesville, VA 22908. Phone: (804) 924-5395. Fax: (804) 982-1071. E-mail: jtp{at}virginia.edu.
Present address: c/o CMHA (NF Division), St. John's, Newfoundland
A1C 5X3, Canada.
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