Tumor suppressor serine/threonine-protein kinase involved in mTORC1 signaling and post-transcriptional regulation. Phosphorylates FOXO3; ERK3/MAPK6; ERK4/MAPK4; HSP27/HSPB1; p53/TP53 and RHEB. Acts as a tumor suppressor by mediating Ras- induced senescence and phosphorylating p53/TP53. Involved in post- transcriptional regulation of MYC by mediating phosphorylation of FOXO3: phosphorylation of FOXO3 leads to promote nuclear localization of FOXO3; enabling expression of miR-34b and miR-34c; 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent MYC translation. Acts as a negative regulator of mTORC1 signaling by mediating phosphorylation and inhibition of RHEB. Part of the atypical MAPK signaling via its interaction with ERK3/MAPK6 or ERK4/MAPK4: the precise role of the complex formed with ERK3/MAPK6 or ERK4/MAPK4 is still unclear; but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPK (ERK3/MAPK6 or ERK4/MAPK4); ERK3/MAPK6 (or ERK4/MAPK4) is phosphorylated and then mediates phosphorylation and activation of MAPKAPK5; which in turn phosphorylates ERK3/MAPK6 (or ERK4/MAPK4). Mediates phosphorylation of HSP27/HSPB1 in response to PKA/PRKACA stimulation; inducing F-actin rearrangement. {ECO:0000269|PubMed:17254968; ECO:0000269|PubMed:17728103; ECO:0000269|PubMed:19166925; ECO:0000269|PubMed:21329882; ECO:0000269|PubMed:9628874}.