Crosstalk Between mTORC1 and cAMP Signaling
Abstract
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 mTORC1 inhibitors is being used for TSC related complication. We have focused our efforts on the molecular mechanisms of negative regulation of mTORC1 by upstream signals. We have shown that mTORC1 is potently inhibited by hormones that stimulating cAMP. We found that cAMP acts through protein kinase A (PKA) to inhibit mTORC1. Our data indicate that PKA phosphorylates Raptor, a subunit if mTORC1, to inhibit mTORC1. We observed the mTORC1 is potently inhibited by osmotic stress and a possible role of the NLK kinase in mTORC1 inhibition. We also discovered that different amino acids stimulate mTORC1 by different mechanisms.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2015
- Accession Number
- ADA623565
Entities
People
- Kun-liang Guan
Organizations
- University of California, San Diego