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Nuclear localization of p85s6k: functional requirement for entry into S phase.
Author(s) -
Reinhard C.,
Fernandez A.,
Lamb N.J.,
Thomas G.
Publication year - 1994
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1994.tb06418.x
Subject(s) - biology , phase (matter) , computational biology , microbiology and biotechnology , physics , quantum mechanics
Immunolocalization of a newly described isoform of p70s6k, termed p85s6k, demonstrated a predominantly nuclear location in rat embryo fibroblasts (REF‐52), a compartment in which growth factor‐mediated phosphorylation of S6 has recently been reported. Microinjection of expression vectors encoding either p85s6k or a fusion protein containing only the putative nuclear localization motifs led to the exclusive accumulation of both products in the nucleus. Consistent with such a localization, microinjection of affinity‐purified anti‐p85s6k IgG into the nucleus, but not the cytoplasm, blocked serum‐induced initiation of DNA synthesis. Co‐injection into the nucleus of the anti‐p85s6k IgG with activated p70s6k, which lacks the antigenic epitope, rescued the S phase block, arguing that the antibody exerts its effects through inhibiting p85s6k function. The results indicate a novel role for S6 phosphorylation in the nucleus distinct from that in the cytoplasm, a role essential for mitogenesis.