Regulation of STAT3 activity by G16-coupled receptors

Wu, Eddy H.T.; Lo, Rico K.H.; Wong, Yung Hou

doi:10.1016/s0006-291x(03)00451-0

Cited by 50 publications

(46 citation statements)

References 31 publications

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“…(iii) Activation of G i -dependent events, known to be exclusively triggered by ICL3 of CXCR4, is necessary for SDF-1␣-induced Jak/STAT activation. This last hypothesis can be excluded because SDF-1␣-mediated STAT3 activation occurs in the presence of PTX, according to our result and data from the literature (17,18,36,(61)(62)(63).…”

Section: Discussionsupporting

confidence: 77%

Identification of the Cytoplasmic Domains of CXCR4 Involved in Jak2 and STAT3 Phosphorylation

Ahr

Denizot

Robert-Hebmann

et al. 2005

Journal of Biological Chemistry

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The chemokine SDF-1␣ transduces G i -dependent and -independent signals through CXCR4. Activation of Jak2/STAT3, a G i -independent signaling pathway, which plays a major role in survival signals, is known to be activated after SDF-1␣ binding to CXCR4 but the domains of CXCR4 involved in this signaling remain unexplored. Using human embryonic kidney HEK-293 cells stably expressing wild-type or mutated forms of CXCR4, we demonstrated that STAT3 phosphorylation requires the N-terminal part of the third intracellular loop (ICL3) and the tyrosine 157 present at the end of the second intracellular loop (ICL2) of CXCR4. In contrast, neither the conserved Tyr 135 in the DRY motif at the N terminus of ICL2 nor the Tyr 65 and Tyr 76 in the first intracellular loop (ICL1) are involved in this activation. ICL3, which does not contain any tyrosine residues, is needed to activate Jak2. These results demonstrate that two separate domains of CXCR4 are involved in Jak2/ STAT3 signaling. The N-terminal part of ICL3 is needed to activate Jak2 after SDF-1␣ binding to CXCR4, leading to phosphorylation of only one cytoplasmic Tyr, present at the C terminus of ICL2, which triggers STAT3 activation. This work has profound implications for the understanding of CXCR4-transduced signaling.

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Section: Discussionsupporting

confidence: 77%

Identification of the Cytoplasmic Domains of CXCR4 Involved in Jak2 and STAT3 Phosphorylation

Ahr

Denizot

Robert-Hebmann

et al. 2005

Journal of Biological Chemistry

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“…Since expression of G␣ 16 is regulated during human myeloid differentiation as well as following T-cell activation (39), it represents a prime candidate for the regulation of STAT pathways that are often associated with cytokine signaling. We have recently demonstrated that activation of G␣ 16 -coupled formyl peptide and opioid receptor-like receptors leads to the phosphorylation and activation of STAT3 (23). The present study confirms that G␣ 16 , like G␣ o and G␣ i2 (4), is indeed capable of activating STAT3 through a complex mechanism involving multiple intermediates.…”

Section: Activation Of Stat3 By Constitutively Active G␣supporting

confidence: 84%

“…Based on the exclusivity of G␣ 16 expression in hematopoietic cells and the involvement of STAT pathways in both normal and perturbed hematopoiesis (22), phosphorylation of STAT3 via G␣ 16 activation may represent an important pathway for cell differentiation and development in the immune system. Indeed, we have recently shown that G␣ 16 can support receptor-mediated activation of STAT3 in human embryonic kidney 293 (HEK 293) cells (23). In the present study, we examined the mechanism by which G␣ 16 QL, a constitutively active G␣ 16 mutant, stimulated STAT3 in HEK 293 cells and provide evidence for the involvement of various intermediate signaling molecules including c-Src, JAKs, and extracellular signal-regulated kinase (ERK).…”

mentioning

confidence: 92%

Constitutively Active Gα16 Stimulates STAT3 via a c-Src/JAK- and ERK-dependent Mechanism

Cheung²,

Wong

2003

Journal of Biological Chemistry

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“…Besides growth factor receptors, signaling through a variety of GPCRs also leads to Stat3 activation (57)(58)(59). Predominantly, GPCRs that link to either G o or G q subfamily members have been associated with Stat3 activation.…”

Section: Egf Stimulation Results In the Recruitment Of C-src Pyk2mentioning

confidence: 99%