Growth hormone (GH) induces the formation of protein complexes involving Stat5, Erk2, Shc and serine phosphorylated proteins.

The aim of this study was to investigate the interaction of Stat5 with key effector proteins Erk2 and Shc after activation by growth hormone (GH), using Chinese Hamster Ovary (CHO) cells stably expressing the wild type rabbit growth hormone receptor (GHR). In coimmunoprecipitation experiments, we show GH-induced formation of complexes consisting of Stat5a and Erk2, and Stat5a and Stat5b association with the protein adaptor Shc. In CHO cells treated with GH, a rapid association of tyrosine and serine phosphorylated Stat5a with activated Erk2 is observed.

Prolactin: a hormone at the crossroads of neuroimmunoendocrinology.

Prolactin (PRL), secreted by the pituitary, decidua, and lymphoid cells, has been shown to have a regulatory role in reproduction, immune function, and cell growth in mammals. The effects of PRL are mediated by a membrane-bound receptor that is a member of the superfamily of cytokine receptors. Formation of a trimer, consisting of one molecule of ligand and two molecules of receptor, appears to be a necessary prerequisite for biological activity.

N-glycosylation of the prolactin receptor is not required for activation of gene transcription but is crucial for its cell surface targeting.

The functional importance of the three oligosaccharide chains linked to Asn35, Asn80 and Asn108, of the long form of the PRL receptor (PRLR) was investigated by individual or multiple substitutions of asparagyl residues using site-directed mutagenesis and transient transfection of these mutated forms of PRLR in monkey kidney cells, Chinese hamster ovary, and human 293 fibroblast cells that exhibit different levels of protein expression. Scatchard analysis performed on monkey kidney cells revealed that the mutants possess the same affinity for PRL as compared with wild-type PRLR. A strong reduction (90%) of the aglycosylated PRLR expression at the cell surface of monkey kidney or human 293 cells was observed.

Homodimerization of IL-2 receptor beta chain is necessary and sufficient to activate Jak2 and downstream signaling pathways.

Cytokine receptor signaling involves the Jak/Stat pathways. Heterotrimeric IL-2R (alpha, beta, gamma[c] chains) activates Jak1 and Jak3, whereas homodimeric PRLR activates Jak2. The requirements directing such specificity of Jak activation are unknown.

Immune function of prolactin (PRL) and signal transduction by PRL/GH/cytokine receptors: specificity, redundancy and lessons from chimaeras.

Although prolactin (PRL) was originally regarded exclusively as a lactogenic hormone, there are a number of observations that suggest a role for this protein in the regulation of immune responses. The first step in understanding this unexpected function came from the cloning of the prolactin receptor, which was later shown to be a member of the cytokine receptor superfamily. The PRL receptor shares structural analogies with receptors for proteins acting on immune cells, the prototype of which is IL-2.

Tyrosine docking sites of the rat prolactin receptor required for association and activation of stat5.

Prolactin (PRL) interacts with a single chain prolactin-specific receptor of the cytokine receptor superfamily. PRL triggers activation of Jak2 kinase which phosphorylates the PRL receptor itself and the mammary gland factor, Stat5, a member of the family of signal transducers and activators of transcription (Stat). Selection of the particular substrate (Stat 5), that is characterized by transcriptional responses to PRL, has been shown to be determined by specific tyrosine-based motifs common to many cytokine receptors.

Antagonistic properties of human prolactin analogs that show paradoxical agonistic activity in the Nb2 bioassay.

Based on the assumption that the prolactin receptor (PRLR) is activated by PRL-induced sequential dimerization, potential human PRL (hPRL) antagonists were designed that sterically interfere with binding site 2. We previously reported the unexpected agonistic properties of these hPRL analogs in the rat Nb2 bioassay (Goffin, V., Struman, I.

Convergence of signaling transduced by prolactin (PRL)/cytokine chimeric receptors on PRL-responsive gene transcription.

Ligand binding to cytokine receptors rapidly triggers tyrosine phosphorylation of Janus family tyrosine kinases (Jaks) and signal transducers and activators of transcription (Stats). Jak2 activation is mediated by PRL receptor homodimers as well as by receptors for the interleukin (IL)-3, IL-5, and granulocyte macrophage-colony stimulating factor, which share the common beta c-subunit. Otherwise, Jak1 and Jak3 are involved in IL-2 signaling through heterodimerization of the IL-2 receptor-beta (IL-2R beta) and gamma c-chains.

The proline-rich region of the GH receptor is essential for JAK2 phosphorylation, activation of cell proliferation, and gene transcription.

Mutational analysis of the proximal transmembrane region of the cytoplasmic domain of the GH receptor (GHR) allowed us to characterize box 1, a proline-rich sequence of eight amino acids, which has been shown to be critical for signal transduction of many cytokine receptors. Mutants of the box 1 region of the rat GHR were studied for their ability to initiate the phosphorylation of JAK2 and the proliferation of stably transfected BAF B03 cells and also the activation of Spi 2.1 gene transcription in transiently transfected Chinese hamster ovary (CHO) cells.

Prolactin and the immune system.

Prolactin (PRL) is involved in a wide range of physiological effects in several species and its immunoregulatory role has already been well documented. The PRL receptor has been cloned from various species. There are at least two receptor isoforms (short and long) in rats and mice, which differ only in their cytoplasmic domains, generated by alternative splicing of a single gene, although in human only the long form exists.

Receptor domains involved in signal transduction of prolactin and growth hormone.

Prolactin (PRL) and growth hormone (GH) receptors are members of a superfamily that include receptors for a number of cytokines. GH and its receptor form an unusual homodimer consisting of one molecule of GH and two molecules of receptor. A similar homodimer of the PRL receptor is probably required for biological effects to be seen.

DNA strand breakage during physiological apoptosis of the embryonic chick lens: free 3' OH end single strand breaks do not accumulate even in the presence of a cation-independent deoxyribonuclease.

Epithelial cells from the lens equator differentiate into elongated fiber cells. In the final steps of differentiation, the chromatin appears quite condensed and chromatin breakdown into nucleosomes occurs. DNA breaks due to an endodeoxyribonuclease activity corresponding to at least two polypeptides of 30 and 40 kDa have been identified.