A role for JAK2 in mediating cell surface GHR-PRLR interaction

• DOI: 10.7554/elife.89890.2
• Publication Date: 2025-03-17T15:25:12Z
• Authors: Chen Chen; Jing Jiang; Tejeshwar C Rao; Ying Liu; Tatiana T Marquez...; Stuart J Frank; André Leier

Growth hormone (GH) receptor (GHR) and (full-length) prolactin (PRL) (PRLR) are transmembrane class I cytokine receptors that co-exist in various normal cancerous cells. Both respond to their associated ligands predominantly by activating the Janus Kinase 2 (JAK2)-signal transducer activator of transcription (STAT) signaling pathways, both also known initiate receptor-specific JAK2-independent signaling. Together with cognate ligands, these have been pro-tumorigenic effects cancers, including breast cancer (BC). Human GH is bind GHR PRLR, while PRL can only PRLR. A growing body work suggests PRLR form heteromers BC cells, modulating signal transduction. However, dynamics on plasma membrane how could affect respective still need be understood.To this end, we set out unravel spatiotemporal surface human T47D cells γ2A-JAK2 We applied direct stochastic optical reconstruction microscopy (dSTORM) quantified colocalization availability at nanometer scale different time points following treatment PRL. In co-expressing surprisingly observed not but induces a significant loss GHR. lacking or expressing mutant deficient JAK2 binding, downregulation cell membrane-bound GHR, no longer Colocalizations were confirmed proximity ligation (PL) assay.Our results suggest PRLR-GHR interaction, indirect, indispensable for PRL- GH- induced GH-induced PRL-induced increase potential consequences downstream Furthermore, our binding via intracellular domain’s Box1 element crucial regulation one receptor’s ligand-induced activation another receptor. Our findings shed new light reciprocal collective role play regulating