Molecular Endocrinology, Vol 7, 1178-1184, Copyright © 1993 by Endocrine Society

ARTICLES

Roles of extracellular and cytoplasmic domains of the prolactin receptor in signal transduction to milk protein genes

L Lesueur, M Edery, J Paly, PA Kelly and J Djiane
Unite d'Endocrinologie moleculaire, Institut National de la Recherche Agronomique, Jouy-en-Josas, France.

We have previously shown that the long form of the PRL receptor is able to activate milk protein gene transcription. In the present study, we have determined the respective contribution of the extracellular and the intracellular domains of this receptor to transcriptional activation of a milk protein gene by PRL. The membrane-anchored intracellular domain (pTMI) expressed alone was devoid of PRL binding activity, as expected, and did not constitutively stimulate expression of the target gene. The extracellular domain (pE), expressed alone as a soluble receptor form, binds PRL with 10-fold higher affinity than the full-length membrane receptor. This form was also unable to stimulate the expression of the reporter gene. However, expression of both mutants (pE + pTMI) in the same cell partially restored the ability of PRL to activate the beta-lactoglobulin promoter. Replacement of cysteine 184 by a serine in the extracellular domain of the receptor impairs this restoration of the biological response. However, introduction of the same mutation in the full-length receptor did not affect its functional activity. These results indicate that the membrane-anchored cytoplasmic domain of the PRL receptor has no constitutive activity, and that coexpression of individual extracellular and intracellular domains leads to restoration of receptor function. We propose that restoration may be the result of reconstitution of the holoreceptor through disulfide bonding, or it may be the result of interaction of the extracellular region with an external transducing molecule.

This article has been cited by other articles:

				H. Buteau, A. Pezet, F. Ferrag, M. Perrot-Applanat, P. A. Kelly, and M. Edery N-Glycosylation of the Prolactin Receptor Is Not Required for Activation of Gene Transcription but Is Crucial for Its Cell Surface Targeting Mol. Endocrinol., April 1, 1998; 12(4): 544 - 555. [Abstract] [Full Text]