Activation of Ras by Grb2-SOS: Demonstrating an Assembly Role of SH3 Domains

Ali Zarrinpar^1,2, Roby P. Bhattacharyya^1,2, Wendell A. Lim², and Nancy R. Gough^3*

¹Program in Biological Sciences, University of California San Francisco, 600 16th Street, San Francisco, CA 94143-2240, USA.
²Department of Cellular and Molecular Pharmacology and Department of Biochemistry and Biophysics, University of California San Francisco, 600 16th Street, San Francisco, CA 94143-2240, USA.
³Science's STKE, American Association for the Advancement of Science, 1200 New York Avenue, N.W., Washington, DC 20005, USA.

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*Corresponding author. E-mail: ngough{at}aaas.org

Summary

The animation shows a schematic representation of the assembly role of SH3 domain-containing proteins using Grb2 as an example. Growth factor stimulation leads to the activation of receptor tyrosine kinases and to the phosphorylation of the receptor tail and the stimulation of phosphorylation of related adaptor proteins (not shown). The resultant phosphotyrosines form docking sites for the adaptor protein Grb2 (through its SH2 domain). The Grb2 SH3 domains bind proline-rich motifs in SOS, the guanine nucleotide exchange factor for Ras, recruiting SOS to the membrane and colocalizing it with Ras. The resultant stimulation of Ras activates a mitogen-activated protein kinase cascade, leading to cell growth and differentiation. The animation could be useful in demonstrating how different protein domains allow dynamic regulation of protein activity, protein assembly, and protein recruitment, allowing cells to respond to signals from their extracellular environment.

Press "Play" to start the animation and "Reset" to return to the unstimulated state.

This animation was created based on Fig. 2A in the review by Zarrinpar et al. (see below) and was prepared by Cameron Slayden with the scientific oversight of A. Zarrinpar, R. P. Bhattacharyya, and W. A. Lim at the University of California San Francisco, San Francisco, CA.

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Educational Details

Learning Resource Type: Animation

Context: Undergraduate upper division, Graduate, Professional (degree program)

Intended Users: Teacher, learner

Intended Educational Use: Teach, learn

Discipline: Cell biology, molecular biology, structural biology

Keywords: movie, signal transduction, cell proliferation, SH3 domain, phosphorylation, cell signaling

Technical Details

Format: Shockwave Flash Object (swf file)

Size: 20 kb

Requirements: Macromedia Flash 5 (http://www.macromedia.com/downloads/)

Related Resources

Review: A. Zarrinpar, R. P. Bhattacharyya, W. A. Lim, The structure and function of proline recognition domains. Sci. STKE 2003, re8 (2003). [Gloss] [Abstract] [Full Text] [Structures]

ST on the Web: Educator Sites (http://stke.sciencemag.org/cgi/ul/sigtransUl;CAT_9)--BioSciEdNet (BEN) Portal

Limits for Use

Cost: Free

Rights: This material may be downloaded, printed, linked to, and/or redistributed without modification for noncommercial, course teaching purposes only, provided credit to STKE is included by listing the citation for the teaching resource.

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Citation: A. Zarrinpar, R. P. Bhattacharyya, W. A. Lim, N. R. Gough, Activation of Ras by Grb2-SOS: Demonstrating an Assembly Role of SH3 Domains. Sci. STKE 2003, tr1 (2003).

© 2003 American Association for the Advancement of Science