Fig. 1: MTORC1 complex is one of the master regulators of cell growth and metabolism. | Modern Pathology

Fig. 1: MTORC1 complex is one of the master regulators of cell growth and metabolism.

From: Oncocytic renal neoplasms with diffuse keratin 7 immunohistochemistry harbor frequent alterations in the mammalian target of rapamycin pathway

Fig. 1

Its activity is regulated by the tuberous sclerosis complex (TSC). TSC is a GTPase activating protein (GAP). The GTPase protein RHEB regulates MTOR by increasing its activity. TSC inactivates RHEB and in turn downregulates MTOR activity. AMPK activates TSC complex, which in turn regulates the activity of MTOR. AKT signaling cascade is activated by receptor tyrosine kinases which induce production of phosphatidylinositol (3,4,5) trisphosphates (PIP3) by phosphoinositide 3-kinase (PI3K). NF1 protein, neurofibromin 1, negatively regulates RAS proteins through GTPase activity. Ras is an activator of the phosphatidylinositol-3-kinase (PI3K)-AKT pathway. The tumor suppressor phosphatase and tensin homolog (PTEN) inhibits AKT activity by dephosphorylating PIP3. AKT regulates cell growth through its effects on the TSC1/TSC2 complex and MTORC signaling.

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