Pleckstrin homology domain leucine-rich repeat protein phosphatases set the amplitude of receptor tyrosine kinase output

This work unveils a previously unidentified function of the tumor suppressor pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP) in inhibiting oncogenic signaling by suppressing the steady-state levels of receptor tyrosine kinases such as the EGF receptor. Specifically, PHLPP modifies the histone code to control the transcription of receptor tyrosine kinases. This epigenetic function can account for the upregulation of receptor tyrosine kinases in the multiple cancer types where PHLPP function is compromised