PDGFRs are critical for PI3K/Akt activation and negatively regulated by mTOR.

PDGFRs are critical for PI3K/Akt activation and negatively regulated by mTOR. Research Abstract Details 

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PDGFRs are critical for PI3K/Akt activation and negatively regulated by mTOR. Abstract Text:

Hongbing Zhang,Natalia Bajraszewski,Erxi Wu,Hongwei Wang,Annie P Moseman,Sandra L Dabora,James D Griffin,David J Kwiatkowski,

The receptor tyrosine kinase/PI3K/Akt/mammalian target of rapamycin (RTK/PI3K/Akt/mTOR) pathway is frequently altered in tumors. Inactivating mutations of either the TSC1 or the TSC2 tumor-suppressor genes cause tuberous sclerosis complex (TSC), a benign tumor syndrome in which there is both hyperactivation of mTOR and inhibition of RTK/PI3K/Akt signaling, partially due to reduced PDGFR expression. We report here that activation of PI3K or Akt, or deletion of phosphatase and tensin homolog (PTEN) in mouse embryonic fibroblasts (MEFs) also suppresses PDGFR expression. This was a direct effect of mTOR activation, since rapamycin restored PDGFR expression and PDGF-sensitive Akt activation in Tsc1-/- and Tsc2-/- cells. Akt activation in response to EGF in Tsc2-/- cells was also reduced. Furthermore, Akt activation in response to each of EGF, IGF, and PMA was reduced in cells lacking both PDGFRalpha and PDGFRbeta, implying a role for PDGFR in transmission of growth signals downstream of these stimuli. Consistent with the reduction in PI3K/Akt signaling, in a nude mouse model both Tsc1-/- and Tsc2-/- cells had reduced tumorigenic potential in comparison to control cells, which was enhanced by expression of either active Akt or PDGFRbeta. In conclusion, PDGFR is a major target of negative feedback regulation in cells with activated mTOR, which limits the growth potential of TSC tumors.

PDGFRs are critical for PI3K/Akt activation and negatively regulated by mTOR. Publishing Authors By Initials

H Zhang,N Bajraszewski,E Wu,H Wang,AP Moseman,SL Dabora,JD Griffin,DJ Kwiatkowski,

For similar proteins: neoplasm proteins: tumor suppressor proteins research abstracts see: proteins: neoplasm proteins: tumor suppressor proteins research

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PDGFRs are critical for PI3K/Akt activation and negatively regulated by mTOR. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: The Journal of clinical investigation

VOLUME: 117

Page Numbers: 730-8

Journal Abbreviation: J. Clin. Invest.

ISSN: 0021-9738

DAY: 8

MONTH: 02

YEAR: 2007

PDGFRs are critical for PI3K/Akt activation and negatively regulated by mTOR. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7802877

PDGFRs are critical for PI3K/Akt activation and negatively regulated by mTOR. Keywords Mesh Terms:

KEYWORDS: Tumor Suppressor Proteins

MESH TERMS: genetics

Chemical & Substance for Abstract: PDGFRs are critical for PI3K/Akt activation and negatively regulated by mTOR. Information

Substance Name: Proto-Oncogene Proteins c-akt

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for PDGFRs are critical for PI3K/Akt activation and negatively regulated by mTOR.

AFFILIATION: Department of Physiology, National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China. hbzhang2006@gmail.com

Country: United States

AGENCY: United States NINDS

GRANT: NS31535

ACRONYM: NS

MEDLINETA: J Clin Invest

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