{'fraction_non_alphanumeric': 0.019255455712451863, 'fraction_numerical': 0.010911424903722721, 'mean_word_length': 4.950381679389313, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Phosphatidic Acid and Mechanical Stimuli Activate mTOR Signaling via an ERK‐independent Mechanism

Signaling by mTOR is both necessary and sufficient for the induction of hypertrophy in response to increased mechanical loading. Recently it has been suggested that mechanical stimuli (MS) induce mTOR signaling via a mechanism that is dependent on phosphatidic acid (PA). The mechanism via which PA activates mTOR signaling is not clear, but at least two models have been proposed; 1) direct binding of PA to mTOR, or 2) PA‐induced activation of ERK which then stimulates mTOR. In order to more clearly define the role of ERK in the regulation of mTOR by PA and MS, we first performed experiments in which C2C12 myoblasts were stimulated with exogenous PA. The results indicated that exogenous PA was sufficient to induce signaling through both ERK and mTOR, however, inhibition of ERK with UO126 did not prevent the ability of PA to induce mTOR signaling. Next, we performed experiments in which mouse EDL muscles were subjected to intermittent stretch as a source of MS. The results indicated that MS was sufficient to induce an increase in PA, as well as, signaling through both ERK and mTOR. Similar to the results observed with exogenous PA, inhibiting ERK with UO126 did not prevent the ability of MS to induce mTOR signaling. Taken together, these results indicate that both exogenous PA and MS induce mTOR signaling through an ERK‐independent mechanism that potentially involves a direct interaction of PA with mTOR. Support: NIH grant AR057347 to TAH