Home  About us  Contact
 

JAK Activation (jak + activation)

Distribution by Scientific Domains
Medical Sciences100%

Selected Abstracts

Chemokines integrate JAK/STAT and G-protein pathways during chemotaxis and calcium flux responses

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2003
Silvia
Abstract The JAK/STAT (Janus kinase / signaling transducer and activator of transcription) signaling pathway is implicated in converting stationary epithelial cells to migratory cells. In mammals, migratory responses are activated by chemoattractant proteins, including chemokines. We found that by binding to seven-transmembrane G-protein-coupled receptors, chemokines activate the JAK/STAT pathwayto trigger chemotactic responses. We show that chemokine-mediated JAK/STAT activation is critical for G-protein induction and for phospholipase C-, dependent Ca2+ flux; in addition, pharmacological inhibition of JAK or mutation of the JAK kinase domain causes defects in both responses. Furthermore, G,i association with the receptor is dependent on JAK activation, andthe chemokine-mediated Ca2+ flux that requires phospholipase C-, activity takes place downstream of JAK kinases. The chemokines thus employ a mechanism that links heterologous signaling pathways , G proteins and tyrosine kinases , in a network that may be essential for mediating their pleiotropic responses. [source]

Ras and Signal Transducer and Activator of Transcription (STAT) Are Essential and Sufficient Downstream Components of Janus Kinases in Cell Proliferation

CANCER SCIENCE, Issue 5 2000
Rumiko Mizuguchi
Cytokines exert their activities in cell growth and differentiation by binding specific cell membrane receptors. Janus kinases (JAKs) are cytoplasmic protein tyrosine kinases that physically interact with intracellular domains of the cytokine receptors and they play crucial roles in transducing signals triggered by the cytokine-receptor interaction. We have previously shown that conditional activation of JAK through membrane-proximal dimerization confers cytokine-independence on interleukin-3 (IL-3)-dependent Ba/F3 lymphoid cells and that the cytokine-independent proliferation is completely inhibited by dominant negative Ras. In this work, we demonstrate that ectopic expression of a dominant negative form of Stat5, a major signal transducer and activator of transcription (STAT) expressed in Ba/F3 cells, also inhibits JAK-triggered mitogenesis. In contrast, overexpression of constitutively active Ras or conditional activation of Stat5 by chemical dimerization fails to confer cytokine-independence. However, concomitant activation of ectopic Ras and Stat5 molecules in Ba/F3 cells suffices for cell proliferation in the absence of IL-3. Our results indicate that Ras and STAT are essential and sufficient components of JAK-triggered mitogenesis. Our findings further indicate that the cytokine signal bifurcates into Ras and STAT pathways following JAK activation. [source]

Chemokines integrate JAK/STAT and G-protein pathways during chemotaxis and calcium flux responses

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2003
Silvia
Abstract The JAK/STAT (Janus kinase / signaling transducer and activator of transcription) signaling pathway is implicated in converting stationary epithelial cells to migratory cells. In mammals, migratory responses are activated by chemoattractant proteins, including chemokines. We found that by binding to seven-transmembrane G-protein-coupled receptors, chemokines activate the JAK/STAT pathwayto trigger chemotactic responses. We show that chemokine-mediated JAK/STAT activation is critical for G-protein induction and for phospholipase C-, dependent Ca2+ flux; in addition, pharmacological inhibition of JAK or mutation of the JAK kinase domain causes defects in both responses. Furthermore, G,i association with the receptor is dependent on JAK activation, andthe chemokine-mediated Ca2+ flux that requires phospholipase C-, activity takes place downstream of JAK kinases. The chemokines thus employ a mechanism that links heterologous signaling pathways , G proteins and tyrosine kinases , in a network that may be essential for mediating their pleiotropic responses. [source]

Activation of the JAK/STAT Pathway in Epstein Barr Virus+ -Associated Posttransplant Lymphoproliferative Disease: Role of Interferon-,

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2009
M. Vaysberg
Epstein Barr virus (EBV) is associated with B-cell lymphomas in posttransplant lymphoproliferative disease (PTLD). Latent membrane protein 1 (LMP1), the major oncogenic protein of EBV, promotes tumorigenesis through activation of NF-,B, Erk, p38, JNK and Akt. The Jak/STAT signal transduction pathway is also constitutively active in PTLD-associated EBV+ B-cell lymphomas. Here we determine the mechanism of Jak/STAT activation in EBV+ B-cell lymphomas and the role of LMP1 in this process. Immunoprecipitation studies revealed no direct interaction of LMP1 and JAK3, but known associations between JAK3 and common gamma chain, and between LMP1 and TRAF3, were readily detected in EBV+ B cell lines from patients with PTLD. An inducible LMP1 molecule expressed in EBV, BL41 Burkitt's cells demonstrated STAT activation only after prolonged LMP1 signaling. While LMP1 induced IFN-, production in BL41 cells, IFN-, receptor blockade and IFN-, neutralization prior to LMP1 activation markedly decreased STAT1 activation and expression of LMP1-driven IFN-, inducible genes. Understanding the mechanisms by which EBV induces cellular signal transduction pathways may facilitate development of new treatments for PTLD. [source]