p85S6K1

p85S6K1 is an isoform of ribosomal protein S6 kinase 1 (S6K1), a serine/threonine kinase in the AGC kinase family. The best-characterized S6K1 species runs at about 70 kDa (p70S6K1). In some reports, the designation p85S6K1 is used to refer to an 85-kilodalton form of S6K1. The exact origin of this 85 kDa species varies; it may arise through alternative splicing, alternate translation initiation, or post-translational processing, and is not universally defined across tissues or species.

Like other S6K1 proteins, p85S6K1 phosphorylates substrates to promote protein synthesis and cell growth. The kinase acts downstream of the mTORC1 complex and responds to growth factors, nutrients, and energy status. The best-known substrate is the ribosomal protein S6, but several other translation regulators and signaling proteins are targets.

Activation of S6K1 involves multiple phosphorylation events. mTORC1 signaling contributes to activating phosphorylation, often in conjunction with PDK1, which further primes the kinase. Once active, S6K1 participates in feedback inhibition of insulin/IGF-1 signaling by phosphorylating IRS family proteins, thereby modulating upstream PI3K activity.

p85S6K1 shares the characteristic architecture of S6Ks, including a catalytic kinase domain and a C-terminal regulatory region that mediates substrate interactions and localization. Activation typically occurs in the cytoplasm, with translocation to other compartments possible under certain conditions.

Alterations in S6K1 signaling are implicated in cancer, metabolic disease, and aging. Pharmacological inhibition or genetic suppression of S6K1 has been explored in research as a means to modulate mTOR pathway activity.