Premium
Role of Cyclophilins in Somatolactogenic Action
Author(s) -
RYCYZYN MICHAEL A.,
CLEVENGER CHARLES V.
Publication year - 2000
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2000.tb05416.x
Subject(s) - action (physics) , chemistry , physics , quantum mechanics
A bstract : Prolactin (PRL) and growth hormone (GH) are members of the somatolactogenic hormone family, the pleiotropic actions of which are necessary for vertebrate growth and mammary differentiation. The basis for the specific function of these hormones has remained uncertain; however, their action is associated with internalization and translocation into the nucleus. A yeast two‐hybrid screen identified an interaction between PRL and cyclophilin B (CypB), a peptidyl prolyl isomerase (PPI) found in the endoplasmic reticulum (ER), extracellular space, and nucleus. The interaction between CypB and PRL/GH was confirmed in vitro and in vivo through the use of recombinant proteins and coimmunoprecipitation studies. The exogenous addition of CypB potentiated the proliferation of PRL‐ and GH‐dependent cell lines 18‐ and 40‐fold, respectively. The potentiation of PRL action by CypB was accompanied by a dramatic increase in the nuclear retrotranslocation of PRL. Immunogold electron microscopy has revealed this retrotransport to occur via a vesicular pathway. A CypB mutant, termed CypB‐NT, was generated that lacked the putative wild‐type N‐terminal nuclear localization sequence. Although CypB‐NT demonstrated levels of PRL binding and PPI activity equivalent to wild‐type CypB, it was incapable of mediating the nuclear retrotranslocation of PRL or enhancing PRL‐driven proliferation. These studies reveal CypB as an important chaperone facilitating the nuclear retro‐transport and action of the somatolactogenic hormone family.