Identification of JAK protein tyrosine kinases as signaling molecules for prolactin. Functional analysis of prolactin receptor and prolactin-erythropoietin receptor chimera expressed in lymphoid cells.

Abstract

The mechanism of action of prolactin (PRL) was studied in murine lymphoid BAF‐3 cells transfected with either the long form of the PRL receptor (PRL‐R), or a chimeric receptor consisting of the extracellular domain of the PRL‐R and the transmembrane and intracellular domain of the erythropoietin receptor (PRL/EPO‐R). PRL sustained normal and long‐term proliferation of BAF‐3 cells expressing either the PRL‐R or the hybrid PRL/EPO‐R. Upon [125I]PRL cross‐linking, both types of BAF‐3 transfectants were shown to express two [125I]PRL cross‐linked species differing in size by 20 kDa. These cross‐linked complexes, after denaturation, were recognized by antibody against the PRL‐R, indicating that they contain the transfected receptor. PRL induced rapid and transient tyrosine phosphorylation of both the PRL‐R and the PRL/EPO‐R in BAF‐3 transfectants. Furthermore, PRL induced rapid tyrosine phosphorylation of the Janus kinase 2 (JAK2) which was already physically associated with the PRL‐R or the PRL/EPO‐R in the absence of ligand. JAK1 was also associated with PRL‐R and PRL/EPO‐R in the absence of ligand. However, only in BAF‐3 cells expressing the PRL‐R does PRL induce rapid and transient tyrosine phosphorylation of JAK1. These results demonstrate that JAK protein tyrosine kinases couple PRL binding to tyrosine phosphorylation and proliferation.

Colony‐stimulating factors and interferon‐γ activate a protein related to MGF‐Stat 5 to cause formation of the differentiation‐induced factor in myeloid cells

“…The prolactin receptor activates Jak 2 in vivo [29][30][31][32]. GM-CSF and IFN-y receptors are both capable of activating Jak2 [33][34][35].…”

Janus kinases: components of multiple signaling pathways

“…Also, JAK2 and TYK2 are activated upon IL-12 stimulation and are proposed to play a critical role in IL-12 mediated T-cell di erentiation (Bacon et al, 1995). Similarly, JAK kinases have been shown to play a key role in the signal transduction pathways initiated in response to stimulation by growth hormone (Argetsinger et al, 1993), prolactin Dusanter-Fourt et al, 1994) and G-CSF (Nicholson et al, 1994;Shimoda et al, 1994). The interferons also transduce their signals via the JAK kinases, JAK1, JAK2 and TYK2 Velazquez et al, 1992Velazquez et al, , 1995Watling et al, 1993).…”

Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) stimulates primitive and definitive erythropoiesis in mouse embryos expressing hGM-CSF receptors but not erythropoietin receptors

“…8,25 The hGMR and these receptors activate signaling molecules similar to EPOR, such as Janus kinase 2 and signal transducer and activator of transcription 5. [33][34][35][36][37] Therefore, cytokine receptors, which activate a set of downstream signaling molecules similar to those activated by EPOR, may be able to substitute for EPOR. On the other hand, Wessely et al 38 analyzed the effect of hGMR signal on erythropoiesis using avian hematopoietic progenitors and found that hGMR only partially substituted for the activities of EPOR.…”