Tec tyrosine kinase links the cytokine receptors to PI-3 kinase probably through JAK

Takahashi-Tezuka, Mariko; Hibi, Masahiko; Fujitani, Yoshio; Fukada, Toshiyuki; Yamaguchi, Takuya; Hirano, Toshio

doi:10.1038/sj.onc.1201071

Cited by 87 publications

(61 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further, it has been shown that the rGH signal can be transmitted to the actin cytoskeleton via Jak, p125 FAK , and tensin, and the actin polymerization produced by GH stimulation occurs due to the PI-3 kinase activation (41). Moreover, it has been suggested the indirect association of Jak2 with p125 FAK occurs via Tec and PI-3 kinase (41,50,51). In the present study we found that the physical association between Jak2 and p125FAK could be mediated via STAT3.…”

Section: Discussionsupporting

confidence: 52%

Regulation of Neutrophil Adhesion by Pituitary Growth Hormone Accompanies Tyrosine Phosphorylation of Jak2, p125FAK, and Paxillin

Ryu

Lee

Kim

et al. 2000

The Journal of Immunology

View full text Add to dashboard Cite

Neutrophil adhesion is fundamentally important during the onset of inflammatory responses. The adhesion signaling pathways control neutrophil arrest and extravasation and influence neutrophil shape and function at sites of inflammation. In the present study the intracellular signaling pathways for the adhesion of human neutrophils by pituitary growth hormone (GH) were examined. Pituitary GH triggered the tyrosine phosphorylation of Janus kinase 2 (Jak2) and STAT3 in neutrophils. In addition, pituitary GH treatment resulted in the morphological changes and the tyrosine phosphorylation of focal adhesion kinase (p125FAK) and paxillin. Preincubation with genistein, a tyrosine kinase inhibitor, blocked the GH-stimulated adhesion and Jak2, STAT3, p125FAK, and paxillin phosphorylation. Confocal microscopy revealed that pituitary GH stimulates the focal localization of p125FAK, paxillin, phosphotyrosine, and filamentous actin filament into the membrane rufflings and uropods of human neutrophils. Immunoprecipitation experiments revealed a physical association of Jak2 with p125FAK via STAT3 in vivo. Also an in vitro kinase assay showed an augmentation of p125FAK autophosphorylation as a result of pituitary GH treatment. These results suggest that pituitary GH modulates neutrophil adhesion through tyrosine phosphorylation of Jak2, p125FAK, and paxillin and actin polymerization.

show abstract

Section: Discussionsupporting

confidence: 52%

Regulation of Neutrophil Adhesion by Pituitary Growth Hormone Accompanies Tyrosine Phosphorylation of Jak2, p125FAK, and Paxillin

Ryu

Lee

Kim

et al. 2000

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Btk interacts with the TIR domain of TLRs as well as with downstream molecules such as MyD88, MAL, and IL-1R-associated kinase-1, but the precise nature of these interactions is not well defined. Btk is probably activated through Src kinases although other tyrosine kinases such as PI3K and Jak1 have also been shown to phosphorylate members of the Btk family (23). Because FAK has been demonstrated to be an upstream activator of Bmx/Etk in endothelial cells (24), it is conceivable that FAK might lead to the recruitment of MyD88 via the activation of a member of the Btk family of kinases and further downstream signaling to MAPKs, AP-1, and NF-B.…”

Section: Discussionmentioning

confidence: 99%

Cross Talk between MyD88 and Focal Adhesion Kinase Pathways

Zeisel

Druet

Sibilia

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

Focal adhesion kinase (FAK) is a nonreceptor protein tyrosine kinase involved in signaling downstream of integrins, linking bacterial detection, cell entry, and initiation of proinflammatory response through MAPKs and NF-κB activation. In this study, using protein I/II from Streptococcus mutans as a model activator of FAK, we investigated the potential link between FAK and TLR pathways. Using macrophages from TLR- or MyD88-deficient mice, we report that MyD88 plays a major role in FAK-dependent protein I/II-induced cytokine release. However, response to protein I/II stimulation was independent of TLR4, TLR2, and TLR6. The data suggest that there is a cross talk between FAK and MyD88 signaling pathways. Moreover, MyD88-dependent, LPS-induced IL-6 secretion by human and murine fibroblasts required the presence of FAK, confirming that MyD88 and FAK pathways are interlinked.

show abstract

“…Upon cytokine stimulation, Tec associates with gp 130, a signal transducer of the IL-6 family (Matsuda et al, 1995), and c-kit (Tang et al, 1994). Furthermore, it has been revealed that Tec links cytokine receptors to phosphatidylinositol 3-kinase through JAKs (Janus kinases) (Takahashi-Tezuka et al, 1997). Thus, it is highly possible that Tec plays an important role in cytokinemediated signalings.…”

Section: Introductionmentioning

confidence: 99%

Tec is involved in G protein-coupled receptor- and integrin-mediated signalings in human blood platelets

et al. 1998

View full text Add to dashboard Cite

Tec is a non-receptor type tyrosine kinase which is tyrosine phosphorylated and activated upon stimulation of hematopoietic cells with various cytokines. The role of Tec in G protein-coupled receptor-and integrin-mediated signalings has not been elucidated. We therefore investigated the regulation of Tec in human blood platelets. Tec was rapidly tyrosine phosphorylated in response to platelet agonists which activate G proteincoupled receptors such as thromboxane A 2 analog (U46619), thrombin, and thrombin receptor activating peptide (TRAP). TRAP-induced phosphorylation in Tec was signi®cantly reduced under the conditions which abrogate ®brinogen binding to GP IIb ± IIIa and subsequent platelet aggregation. However, TRAP induced signi®cant levels of the phosphorylation even under these conditions and also in thrombasthenic platelets which lack functional GP IIb ± IIIa molecules, suggesting that activation of G-protein-coupled receptor causes the phosphorylation. To clarify whether integrin engagement by itself causes the phosphorylation in Tec, we examined the state of the phosphorylation in platelets activated by integrin engagement. Platelet adhesion to immobilized ®brinogen or collagen induced signi®cant levels of the phosphorylation. Furthermore, Tec was translocated to cytoskeleton in response to TRAP in a manner dependent on platelet aggregation, suggesting that Tec can be a component of integrin-mediated signalings. These results collectively indicate that Tec is involved in G protein-coupled receptor-and integrin-mediated signalings in human blood platelets.

show abstract

Tec tyrosine kinase links the cytokine receptors to PI-3 kinase probably through JAK

Cited by 87 publications

References 60 publications

Regulation of Neutrophil Adhesion by Pituitary Growth Hormone Accompanies Tyrosine Phosphorylation of Jak2, p125FAK, and Paxillin

Regulation of Neutrophil Adhesion by Pituitary Growth Hormone Accompanies Tyrosine Phosphorylation of Jak2, p125FAK, and Paxillin

Cross Talk between MyD88 and Focal Adhesion Kinase Pathways

Tec is involved in G protein-coupled receptor- and integrin-mediated signalings in human blood platelets

Contact Info

Product

Resources

About