Requirement of nuclear prolactin for interleukin-2--stimulated proliferation of T lymphocytes.
Prolactin (PRL) is necessary for the proliferation of cloned T lymphocytes in response to interleukin-2 (IL-2). Translocation of PRL into the nucleus occurs during IL-2--stimulated mitogenesis. Therefore, the function of intranuclear PRL in T cell proliferation was tested. Eukaryotic expression vectors were prepared to express wild-type PRL [PRL(WT)], PRL that lacks the signal sequence for translocation into the endoplasmic reticulum [PRL(ER-)], and chimeric PRL in which the signal peptide was replaced with the sequence that directs the nuclear translocation of the SV40 large T antigen [PRL(NT+)]. Expression of these constructs in a T cell line (Nb2) responsive to PRL and IL-2 resulted in localization of PRL in the extracellular milieu, cytoplasm, or nucleus, respectively. Stimulation with IL-2 alone resulted in a five- to tenfold increase in the incorporation of [3H]thymidine by cells expressing PRL(NT+) or PRL(WT) as compared to PRL(ER-) or the parental Nb2 cells. Only the PRL(NT+) clone proliferated continuously with IL-2 stimulation in the presence of antiserum to PRL. These results demonstrate that nuclear PRL is necessary for IL-2--stimulated proliferation and suggest that a peptide hormone can function in the nucleus without binding to its cell surface receptor.
Clevenger
C V
CV
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104.
Altmann
S W
SW
Prystowsky
M B
MB
D000595:Amino Acid Sequence; D000818:Animals; D001693:Biological Transport, Active; D002453:Cell Cycle / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D004357:Drug Synergism; D005822:Genetic Vectors; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008969:Molecular Sequence Data; D011388:Prolactin / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D014162:Transfection
D007376:Interleukin-2; D011388:Prolactin