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PTEN is Necessary for Human Sprouty 2 Mediated Inhibition of Cell Proliferation
Author(s) -
Singh Rakesh K,
Edwin Francis,
Endersby Raelene,
Baker Suzanne J,
Patel Tarun B
Publication year - 2006
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.20.5.lb112-c
Subject(s) - pten , tensin , protein kinase b , cell growth , phosphatase , cancer research , phosphorylation , pi3k/akt/mtor pathway , chemistry , cell , microbiology and biotechnology , biology , signal transduction , biochemistry
Human Sprouty 2 (hSPRY2) inhibits the proliferation of a number of different cell types. However, the mechanisms involved in the antiproliferative actions of hSPRY2 remain to be elucidated. Because Phosphatase and tensin homologue deleted on chromosome ten (PTEN) content in hSPRY2 expressing cells is elevated, we postulated that the anti‐proliferative actions of hSPRY2 are mediated by an increase in PTEN content and activity. Here we demonstrate that despite an increase in PTEN turnover, hSPRY2 increases the amount of PTEN by increasing the level of PTEN transcript. hSPRY2 also decreases the phosphorylation PTEN which may also contribute to increase in its activity. The elevated PTEN activity is reflected by decreased activation of Akt by epidermal growth factor and serum in hSPRY2 expressing cells. In primary mouse embryonic fibroblasts from Pten loxP/loxP mice, the knock out of Pten obliterated the ability of hSPRY2 to decrease agonist stimulated Akt activation and cell proliferation. Likewise, in HeLa cells, knock down of PTEN by siRNA approaches also abrogated the anti‐proliferative actions of hSPRY2. Therefore, we conclude that hSPRY2 mediates its anti‐proliferative actions by altering PTEN content and perhaps the phosphorylation status of PTEN. Supported by NIH grants HL48308 and GM073181(to TBP), NS44172, and CA096832 (to SJB) and the American Lebanese and Syrian Associated Charities