A Caltech Library Service

Coordinate activation of c-Src by SH3- and SH2-binding sites on a novel p130^(Cas)-related protein, Sin

Alexandropoulos, Konstantina and Baltimore, David (1996) Coordinate activation of c-Src by SH3- and SH2-binding sites on a novel p130^(Cas)-related protein, Sin. Genes and Development, 10 (11). pp. 1341-1355. ISSN 0890-9369. doi:10.1101/gad.10.11.1341.

[img] PDF - Published Version
Creative Commons Attribution.


Use this Persistent URL to link to this item:


To understand how protein-protein interactions mediated by the Src-SH3 domain affect c-Src signaling, we screened for proteins that interact with the Src-SH3. We found a novel protein, Sin (Src interacting or signal integrating protein), that binds to Src-SH3 with high affinity, contains numerous tyrosine residues in configurations suggestive of SH2-binding sites, and is related to the v-Src substrate p130^(Cas). In cotransfection assays, a small fragment of Sin retaining the Src-SH3-binding site and one tyrosine-containing motif induced c-Src activation as measured by a transcriptional reporter. Phosphorylation of the peptide on tyrosine by c-Src, as a consequence of Src-SH3 binding, was necessary for its stable interaction with c-Src in vivo and for transcriptional activation. Phosphorylation of multiple tyrosine-containing motifs found on Sin correlated with c-Crk and cellular phosphoprotein binding to Sin as well as increased c-Src activity. These data suggest that (1) SH2 and SH3 ligand sites on Sin cooperatively activate the signaling potential of c-Src, (2) Sin acts as both an activator and a substrate for c-Src, and (3) phosphorylated Sin may serve as a signaling effector molecule for Src by binding to multiple cellular proteins.

Item Type:Article
Related URLs:
URLURL TypeDescription
Baltimore, David0000-0001-8723-8190
Additional Information:© 1996 by Cold Spring Harbor Laboratory Press. Received February 28, 1996; revised version accepted April 12, 1996. We are grateful to D. Shalloway for the Src-expressing vectors, M. Curzo and D. Foster for the luciferase reporter construct, J. Brugge for the mAb 327, B. Mayer for the GST-SH2-expressing constructs, A. Laudano for the anti-pY416 antiserum. We thank B. Mayer, I. Stancovski, C. Roman, and Y. Yamanashi for critically reading the manuscript, and C. Roman and S. Cherry for many helpful discussions. K.A. was supported by National Institutes of Health grant 7F32 CA60458-02. This work was supported by National Institutes of Health grant 2R01 CA51462-08 to D.B. The publication costs of this article were defrayed in part by payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.
Funding AgencyGrant Number
NIH Postdoctoral Fellowship7F32 CA60458-02
NIH2R01 CA51462-08
Subject Keywords:Sin; p130^(Cas); Src activation; Src substrate; Crk
Issue or Number:11
Record Number:CaltechAUTHORS:20200507-111419990
Persistent URL:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:103070
Deposited By: Tony Diaz
Deposited On:08 May 2020 17:57
Last Modified:16 Nov 2021 18:18

Repository Staff Only: item control page