دورية أكاديمية
Crosstalk between mTORC1 and cAMP Signaling
| العنوان: | Crosstalk between mTORC1 and cAMP Signaling |
|---|---|
| المؤلفون: | Guan, Kun-Liang |
| المساهمون: | CALIFORNIA UNIV SAN DIEGO LA JOLLA |
| المصدر: | DTIC |
| سنة النشر: | 2014 |
| المجموعة: | Defense Technical Information Center: DTIC Technical Reports database |
| مصطلحات موضوعية: | Biochemistry, Genetic Engineering and Molecular Biology, Medicine and Medical Research, GENES, PHOSPHORUS TRANSFERASES, ACTIVATION, AMINO ACIDS, CELLS(BIOLOGY), INHIBITION, INHIBITORS, NEOPLASMS, PHOSPHORYLATION, PROTEINS, RECEPTOR SITES(PHYSIOLOGY), TSC GENES, TSC(TUBEROUS SCLEROSIS COMPLEX), MTOR, CAMP, PKA(PROTEIN KINASE A), TSC1, TSC2, MTORC1(MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1), GPCR(G-PROTEIN COUPLED RECEPTORS), TUMORS |
| الوصف: | Mutations in TSC1 and TSC2 genes are responsible for the majority of tuberous sclerosis complex (TSC). The major function of TSC1/2 is to inhibit mTORC1. Therefore, uncontrolled mTORC1 activation is a key molecular basis for TSC and TORC1 inhibitors is being used for TSC related complication. We discovered that mTORC1 can be inhibited by intracellular cAMP. We further found that the protein kinase A (PKA) mediates the effect of cAMP to inhibit mTORC1. Overexpression of the catalytic subunit of PKA leads to reduced mTORC1 activity while inhibition of PKA by pharmacological inhibitors blocks the inhibitory effect of cAMP on mTORC1. Furthermore, we found that cAMP and PKA function to prevent mTOR lysosomal localization, which is a process critical for mTORC1 activation. Our studies reveal a potential mechanism and future research direction how PKA inhibits mTORC1. This project also connects the two major intracellular signaling pathways, cAMP and mTOR, in the regulation of cell growth. ; The original document contains color images. |
| نوع الوثيقة: | text |
| وصف الملف: | text/html |
| اللغة: | English |
| العلاقة: | http://www.dtic.mil/docs/citations/ADA612068Test |
| الإتاحة: | http://www.dtic.mil/docs/citations/ADA612068Test http://oai.dtic.mil/oai/oai?&verb=getRecord&metadataPrefix=html&identifier=ADA612068Test |
| حقوق: | Approved for public release; distribution is unlimited. |
| رقم الانضمام: | edsbas.F11C9EC1 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |