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Eukaryotic initiation factor (eIF4E) phosphorylation is a recognized attribute for enhanced cell growth and proliferation. Our recent data that identified eIF4E as mTORC1 substrate with ability to influence rapamycin response highlights its prospect as a mediator of mTORC1 signaling. Here, we present evidence that eIF4E phosphorylated at S209 interacts with TOS motif of S6 Kinase1 (S6K1). We show that this interaction is sufficient to overcome rapamycin sensitivity and mTORC1 dependence of S6K1. We present data to demonstrate that eIF4E-S6K1 interaction relieves S6K1 of its auto inhibition, otherwise rate limiting for its activation. We go on to identify a highly conserved sequence segment that mediates hydrophobic motif phosphorylation of S6K1 in mTORC2 rather than mTORC1 dependent manner. We also identify a novel eight amino-acid PHLPP1 (Pleckstrin Homology Domain Leucine-rich Repeat Protein Phosphatase) binding region necessary to mediate S6K1 response to serum/growth factor stimulation. Finally, we show that deletion of the PHLPP1 binding region abolishes serum/growth factor stimulatory response without interfering with S6K1 regulation by mTORC1 or mTORC2. Our data identifies eIF4E as a novel TOS binding subunit that realigns mTORC1 signaling to unravel cross talk with other growth promoting signals for accomplishing S6K1 activation.