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Grb2 interacts with SGEF and antagonizes the ability of SGEF to enhance EGF-induced ERK1/2 activation

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Abstract

Previously, we demonstrated that SGEF enhances EGFR stability; however, SGEF-mediated downstream signaling of EGFR is not well understood. Here, we show that SGEF enhances EGF-induced ERK1/2 activation independent of its guanine nucleotide exchange (GEF) activity. We further show that SGEF interacts with Grb2, a critical downstream transducer of EGFR. Surprisingly, we found that interaction of Grb2 to SGEF antagonizes the ability of SGEF to enhance EGF-induced ERK1/2 activation. Taken together, this study reports a novel function of SGEF that excludes GEF and also provides important insights into the complex role of Grb2 in EGFR signal transduction.

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Abbreviations

SGEF:

SH3-containing guanine nucleotide exchange factor

EGFR:

Epidermal growth factor receptor

EGF:

Epidermal growth factor

GEF:

Guanine nucleotide exchange factor

PTB:

Phosphotyrosine binding

SH2:

Src homology 2

SH3:

Src homology 3

Pro:

Proline-rich domain

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Acknowledgments

We thank Dr. Wannian Yang for providing materials. This work was supported by the grants from the National Natural Science Foundation of China (No. 81372770 to J.Z. and Nos. 81172445 and 81372140 to J.W.).

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Correspondence to Jian Wang or Jianguang Zhou.

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Wang, H., Li, S., Li, H. et al. Grb2 interacts with SGEF and antagonizes the ability of SGEF to enhance EGF-induced ERK1/2 activation. Mol Cell Biochem 389, 239–247 (2014). https://doi.org/10.1007/s11010-013-1945-7

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