Homology modeling of rabbit prolactin hormone complexed with its receptor

Halaby, D.; Thoreau, E.; Djiane, Jean; Mornon, Jean‐Paul

doi:10.1002/(sici)1097-0134(199703)27:3<459::aid-prot13>3.0.co;2-k

Cited by 5 publications

(1 citation statement)

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“…This ligand-independent homodimerization process has previously been reported for cytokine receptors [24]. Previous studies have shown that PRL stimulation induces a conformational change in the extracellular domain of the receptor that is necessary for optimum alignment and bonding of residues involved in dimerization [25,26]. This stabilizes the receptor dimer in a conformation that allows activation of cytoplasmic signaling cascades.…”

Section: Dimerization Of the Mutant Prl-r Is Required For Its Constitsupporting

confidence: 60%

Expression by Transgenesis of a Constitutively Active Mutant Form of the Prolactin Receptor Induces Premature Abnormal Development of the Mouse Mammary Gland and Lactation Failure1

Gourdou¹,

Paly²,

Hue-Beauvais³

et al. 2004

Biology of Reproduction

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Prolactin (PRL) initiates signal transduction by inducing homodimerization of PRL receptor (PRL-R). We have previously developed a mutant form of the PRL-R in which a part of the extracellular domain is deleted. This receptor constitutively activates protein gene transcription. We examined the oligomerization of the mutant PRL-R using two differently epitope-tagged receptors in a coimmunoprecipitation assay. It was shown that mutant receptor dimers were formed in a ligand-independent manner, which may explain the constitutive activity on milk protein gene expression. To study the biological activity of this mutant PRL-R on mammary gland development, we generated two lines of transgenic mice expressing the corresponding cDNA specifically in the mammary epithelial cells. For both transgenic lines, the mammary gland of 8-wk-old virgin mice was overdeveloped with numerous dilated ductal and alveolar structures, whereas only a limited duct network was present in wild-type animals at the same age. During pregnancy, the ducts and alveoli of transgenic mice were more developed than those of control animals. At parturition, the transgenic animals failed to lactate and nourish their offspring, and the involution of the mammary gland was strongly delayed. In conclusion, the expression of a constitutively active PRL-R by transgenesis induces a premature and abnormal mammary development and impairs terminal differentiation and milk production at the end of pregnancy.

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Section: Dimerization Of the Mutant Prl-r Is Required For Its Constitsupporting

confidence: 60%