Coordinated regulation of epidermal Growth Factor Signaling by the protein tyrosine phosphatases SHP‐1 and SHP‐2

• Published in: The FASEB journal Vol. 20; no. 5; p. A923
• Main Authors: Wang, Ning, Ding, Ronghua, Frank, Gerald D., Senbonmatsu, Takaaki, Landon, Erwin J, Inagami, Tadashi
• Format: Journal Article
• Language: English
• Published: Federation of American Societies for Experimental Biology 01-03-2006
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.20.5.A923-d

SHP‐1 and SHP‐2 are two SH2 domain‐containing tyrosine phosphatases. They share significant overall sequence identity, but their biological functions are often opposite. SHP‐1 is generally considered as a negative signal transducer while SHP‐2 as a positive one. However, the precise role of each enzyme in shared signaling pathways is not well defined.
Methods
We examined roles of SHP‐1 and SHP‐2 on epidermal growth factor signaling in Coca‐2 cell line expressing both phosphatases by knocking down these enzymes with specificity siRNAs.
Result
Knockdown of either SHP‐1 or SHP‐2 caused significant reduction in the activation of ERK1/2. However, knockdown of both enzymes simultaneously diminished such an effect, suggesting that SHP‐1 and SHP‐2 rely on each other to up‐regulate the ERK1/2 activation. Furthermore, SHP‐1, SHP‐2, and Gab1 formed a signaling complex, and SHP‐1 and SHP‐2 interact with each other. The interaction of SHP‐1 with Gab1 is mediated by SHP‐2 since it was abrogated by knockdown of SHP‐2.
Conclusion
The data revealed that both SHP‐1 and SHP‐2 have a positive role in epidermal growth factor‐induced ERK activation and that they act cooperatively rather than antagonistically
This work was supported by grant HL058205 (to T. Inagami) from the National Institutes of Health.