The recent finding that sheep had long (l-oPRLR) and short (s-oPRLR) prolactin receptors provided new tools to further explore prolactin signaling to target genes. Here we used CHO cells transfected with l-oPRLR or s-oPRLR cDNAs to compare the activation of known key steps of prolactin signaling by the two receptors. We found that prolactin stimulated l-oPRLR tyrosine phosphorylation, although it lacked the last tyrosine residue found in other long prolactin receptors. In addition, l-oPRLR and s-oPRLR both responded to prolactin stimulation by (1) Janus kinase 2 (Jak2) tyrosine phosphorylation, (2) DNA-binding activation of signal transducer and activator of transcription 5 (STAT5), (3) stimulation of transcription from a promoter made of six repeats of STAT5-responsive sequence. However, although it contains STAT5-binding consensus sequences, the ovine beta-lactoglobulin promoter (-4000 to +40) was transactivated by l-oPRLR, but not by s-oPRLR. Taken together, our results indicate that activation of Jak2/STAT5 pathway alone is not sufficient to account for prolactin-induced transcription of this milk protein gene, and that sequences of its promoter, other than STAT5-specific sequences, account for the opposite transcriptional activation capabilities of l-oPRLR and s-oPRLR.

This article has been cited by other articles:

				Y. S. Devi, A. Shehu, C. Stocco, J. Halperin, J. Le, A. M. Seibold, M. Lahav, N. Binart, and G. Gibori Regulation of Transcription Factors and Repression of Sp1 by Prolactin Signaling Through the Short Isoform of Its Cognate Receptor Endocrinology, July 1, 2009; 150(7): 3327 - 3335. [Abstract] [Full Text] [PDF]

				A. M. Corbacho, G. Valacchi, L. Kubala, E. Olano-Martin, B. C. Schock, T. P. Kenny, and C. E. Cross Tissue-specific gene expression of prolactin receptor in the acute-phase response induced by lipopolysaccharides Am J Physiol Endocrinol Metab, October 1, 2004; 287(4): E750 - E757. [Abstract] [Full Text] [PDF]

				J.-C. Lu, P. Scott, G. J. Strous, and L. A. Schuler Multiple Internalization Motifs Differentially Used by Prolactin Receptor Isoforms Mediate Similar Endocytic Pathways Mol. Endocrinol., November 1, 2002; 16(11): 2515 - 2527. [Abstract] [Full Text] [PDF]

				C V Clevenger and J B Kline Prolactin receptor signal transduction Lupus, October 1, 2001; 10(10): 706 - 718. [Abstract] [PDF]

				D. E. Fleenor and M. Freemark Prolactin Induction of Insulin Gene Transcription: Roles of Glucose and Signal Transducer and Activator of Transcription 5 Endocrinology, July 1, 2001; 142(7): 2805 - 2810. [Abstract] [Full Text] [PDF]