Identificador persistente para citar o vincular este elemento: http://hdl.handle.net/10553/48259
Título: Downregulation of the growth hormone-induced Janus kinase 2/signal transducer and activator of transcription 5 signaling pathway requires an intact actin cytoskeleton
Autores/as: Rico-Bautista, Elizabeth
Negrín-Martínez, Ciro
Novoa Mogollón, Francisco 
Fernández-Perez, Leandro 
Flores-Morales, Amilcar 
Clasificación UNESCO: 32 Ciencias médicas
3201 Ciencias clínicas
Palabras clave: Tyrosyl Phosphorylation
Endoplasmic-Reticulum
Cytokine Signaling-2
Protein-Synthesis
Epithelial-Cells, et al.
Fecha de publicación: 2004
Publicación seriada: Experimental cell research 
Resumen: Transient activation of the signal transducers and activators of transcription (STAT) proteins in response to growth hormone (GH) and other type II cytokines plays a pivotal role on specific gene transcription. The negative regulation of STATs seems to be exerted at the GH receptor (GHR)/Janus Kinase (JAK) complex and involves two main mechanisms: (1) the GH-induced ubiquitination/internalization of GHR and (2) the action of SOCS proteins. Since GH regulates cellular cytoskeleton with potential implications in GH signaling, we investigated the effects of actin cytoskeleton disruption on the kinetics of GH-activated GHR/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) signaling pathway. Disruption of the actin-based cytoskeleton with cytochalasin D (CytoD) did not affect the rapid GH induction of JAK2 and STAT5 activities. However, pretreatment of BRL-4 cells with CytoD prolonged both, JAK2/STAT5 tyrosine phosphorylation and STAT5 DNA binding activity, for at least 2 h. Our results demonstrated that the synthesis of the several SOCS proteins (SOCS-1, -2, and -3) was not affected by treatment of the cells with CytoD. On the other hand, the inhibitory actions of SOCS 1, 2, and -3 on GH-induced STAT5 reporter activity were partially blocked by disruption of the cytoskeleton. Disassembly of the actin filaments by CytoD is accompanied by accumulation of ubiquitinated forms of GHR but it does not affect GHR internalization. We conclude that the integrity of the actin cytoskeleton network plays an essential role in the negative regulation of GHR/JAK2/STAT5 signaling pathway by facilitating the GHR ubiquitination/degradation through mechanisms acting downstream SOCS.
URI: http://hdl.handle.net/10553/48259
ISSN: 0014-4827
DOI: 10.1016/j.yexcr.2003.11.017
Fuente: Experimental Cell Research[ISSN 0014-4827],v. 294, p. 269-280
Colección:Artículos
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