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Endogenous Sprouty 2 positively regulates the ERK1/2 and AKT pathways and is necessary for the anti‐apoptotic actions of serum
Author(s) -
Edwin Francis,
Patel Tarun B
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a805-b
Subject(s) - protein kinase b , microbiology and biotechnology , apoptosis , endogeny , phosphorylation , gene silencing , signal transduction , pi3k/akt/mtor pathway , biology , kinase , receptor tyrosine kinase , tyrosine phosphorylation , chemistry , cancer research , endocrinology , biochemistry , gene
Sprouty (SPRY) proteins are regulators of receptor tyrosine kinase signaling and play important role in cell migration, proliferation and during development. However, the role of endogenous SPRY proteins in regulating signaling events at the cellular level is not yet completely understood. Here, we have examined the role of endogenous human SPRY2 (hSPRY2) in the regulation of cellular apoptosis. Silencing of hSPRY2 using small inhibitory RNA (siRNA) in adrenal cortex adenocarcinoma (SW13) cells decreased the amount of EGF receptor and down regulated the activation of AKT and ERK1/2 by both EGF and serum. These changes were accompanied by complete abrogation of the anti‐apoptotic actions of serum. Silencing of hSPRY2 also decreased EGF and serum‐ induced phosphorylation of pro‐apoptotic protein BAD on S112, the RSK1 phosphorylation site and inhibited the activation of p90RSK1 (the immediate downstream substrate of ERK1/2). Moreover, inhibiting both the ERK1/2 and AKT pathways abolished the ability of serum to protect against apoptosis and mimicked the effects of silencing hSPRY2. The reintroduction of hSPRY2 into SW13 cells in which endogenous hSPRY2 had been silenced reestablished the anti‐apoptotic actions of serum. Thus, we conclude that by positively regulating AKT and ERK1/2 pathways, endogenous hSPRY2 is necessary for the anti‐apoptotic actions of serum.