SH3 domains direct cellular localization of signaling molecules

Bar-Sagi, D., Rotin, D., Batzer, A., Mandiyan, V., Schlessinger, J. (July 1993) SH3 domains direct cellular localization of signaling molecules. Cell, 74 (1). pp. 83-91. ISSN 0092-8674 (Print)

DOI: 10.1016/0092-8674(93)90296-3


In this study we describe the cellular distribution of the SH2 and SH3 domains of phospholipase C-gamma (PLC-gamma) and of the adaptor protein GRB2 following their microinjection into living rat embryo fibroblasts. Using immunofluorescence microscopy, we show that a truncated protein composed of the SH2 and SH3 domains of PLC-gamma was localized to the actin cytoskeleton. A similar localization pattern was observed when only the SH3 domain of PLC-gamma was microinjected. In contrast, a truncated protein composed of only the SH2 domains of PLC-gamma exhibited diffuse cytoplasmic distribution. Microinjected GRB2 protein was localized primarily to membrane ruffles, as was GRB2 protein containing SH2 loss-of-function point mutations. Hence, the localization of GRB2 to membrane ruffles does not require interaction with tyrosine-phosphorylated moieties. However, GRB2 proteins with SH3 loss-of-function point mutations exhibited diffuse cytoplasmic distribution. These results indicate that SH3 domains are responsible for the targeting of signaling molecules to specific subcellular locations.

Item Type: Paper
Uncontrolled Keywords: Actins/ metabolism Adaptor Proteins, Signal Transducing Animals Cell Membrane/chemistry Cells, Cultured/chemistry Cytoplasm/chemistry Cytoskeleton/ metabolism Fibroblasts/chemistry GRB2 Adaptor Protein Microscopy, Fluorescence Phospholipase C/ analysis Proteins/ analysis Rats Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Signal Transduction
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > phospholipase C
organs, tissues, organelles, cell types and functions > tissues types and functions > signal transduction
CSHL Authors:
Communities: CSHL labs
Depositing User: Matt Covey
Date: 16 July 1993
Date Deposited: 22 Apr 2016 15:36
Last Modified: 22 Apr 2016 15:36
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