Nuclear localization of lymphocyte-specific protein tyrosine kinase (Lck) and its role in regulating LIM domain only 2 (Lmo2) gene

Venkitachalam, Srividya; Chueh, Fu-Yu; Yu, Chao‐Lan

doi:10.1016/j.bbrc.2011.12.095

Cited by 18 publications

(17 citation statements)

References 25 publications

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“…Moreover, JAK2 is activated by oxidative stress [7], ischemia [7] and hypertonicity [8,9]. Excessive JAK2 activity may lead to development of malignancy and the gain of function mutation V617F JAK2 presumably predisposes to the development of myeloproliferative disease [10,11,12,13]. Conversely JAK2 inhibitors are considered for the treatment of myeloproliferative disorders [14,15,16,17,18,19].…”

Section: Introductionmentioning

confidence: 99%

Upregulation of Peptide Transporters PEPT1 and PEPT2 by Janus Kinase JAK2

Hosseinzadeh

Luo

Bhavsar

et al. 2013

Cell Physiol Biochem

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Background/Aims: Janus-activated kinase-2 JAK2 participates in the signaling of several hormones including growth hormone, fosters tumor growth and modifies the activity of several Na⁺ coupled nutrient transporters. Peptide uptake into intestinal and tumor cells is accomplished by electrogenic peptide transporters PEPT1 and PEPT2. The present study thus explored whether JAK2 contributes to the regulation of PEPT1 and PEPT2 activity. Methods: cRNA encoding either PEPT1 or PEPT2 was injected into Xenopus oocytes with or without additional injection of cRNA encoding wild type JAK2, constitutively active ^V617FJAK2 or inactive ^K882EJAK2. The current created by the dipeptide glycine-glycine (I_gly-gly) was determined by dual electrode voltage clamp and taken as measure for electrogenic peptide transport. Results: No appreciable I_gly-gly was observed in water injected oocytes. In PEPT1 or PEPT2 expressing oocytes I_gly-gly was significantly increased by additional coexpression of JAK2. As shown in PEPT1 expressing oocytes, I_gly-gly without significantly modifying the concentration required for halfmaximal I_gly-gly (K_M). Following disruption of carrier insertion with brefeldin A (5 µM) I_gly-gly declined similarly fast in Xenopus oocytes expressing PEPT1 with JAK2 and in Xenopus oocytes expressing PEPT1 alone. In oocytes expressing both, PEPT1 and ^V617FJAK2, I_gly-gly was gradually decreased by JAK2 inhibitor AG490 (40 µM). According to Ussing chamber experiments pharmacological JAK2 inhibition similarly decreased I_gly-gly in mouse intestine. Conclusion: Regulation of the peptide transporters PEPT and PEPT2 does involve the Janus-activated kinase-2 JAK2.

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Section: Introductionmentioning

confidence: 99%

Upregulation of Peptide Transporters PEPT1 and PEPT2 by Janus Kinase JAK2

Hosseinzadeh

Luo

Bhavsar

et al. 2013

Cell Physiol Biochem

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“…Light microscopy was used to ensure cell rupture before proceeding to the next step. The nuclear fraction was collected by differential centrifugation as described previously ( 19 ). Fraction purity was verified by immunoblotting of specific markers.…”

Section: Methodsmentioning

confidence: 99%

“…Our previous study demonstrated that, in mouse LSTRA leukemia, Lck upregulated the expression of the LIM domain only 2 gene through direct binding to its promoter region ( 19 ). We further provided evidence supporting the mouse LSTRA leukemic cell line as a model for the aggressive form of human large granular lymphocyte leukemia ( 20 ).…”

Section: Introductionmentioning

confidence: 99%

Nuclear lymphocyte-specific protein tyrosine kinase and its interaction with CR6-interacting factor 1 promote the survival of human leukemic T cells

et al. 2015

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Overexpression and hyperactivation of lymphocyte-specific protein tyrosine kinase (Lck) have been associated with leukemia development. We previously showed that, other than its known function as a cytoplasmic signal transducer, Lck also acts as a nuclear transcription factor in mouse leukemic cells. In the present study, we demonstrated the presence of nuclear Lck in human leukemic T cells and in primary cells. We further established a positive correlation between Lck nuclear localization and its kinase activity. Proteomic analysis identified CR6-interacting factor 1 (CRIF1) as one of the Lck-interacting proteins. CRIF1 and Lck association in the nucleus was confirmed both by immunofluorescence microscopy and co-immunoprecipitation in human leukemic T cells. Close-range interaction between Lck and CRIF1 was validated by in situ proximity ligation assay (PLA). Consistent with the role of nuclear CRIF1 as a tumor suppressor, CRIF1 silencing promotes leukemic T cell survival in the absence of growth factors. This protective effect can be recapitulated by endogenous Lck or reconstituted Lck in leukemic T cells. All together, our results support a novel function of nuclear Lck in promoting human leukemic T cell survival through interaction with a tumor suppressor. It has important implications in defining a paradigm shift of non-canonical protein tyrosine kinase signaling.

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“…Moreover, leptin has an acute effect on the regulation of food intake, energy expenditure in fish (Li et al, 2010). Previous studies have shown that excessive JAK2 activity may contribute to development of malignancy (Venkitachalam et al, 2012). Pept1 was proved to play important roles in mediating the transportation of peptide-like drugs, such as β-lactam antibiotics and bestatin (an anticancer drug) (Inoue et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

JAK2 Mediates the Regulation of Pept1 Expression by Leptin in the Grass Carp (Ctenopharyngodon idella) Intestine

Luo

Song

et al. 2020

Front. Physiol.

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Oligopeptide transporter 1 (Pept1) is located on the brush border membrane of the intestinal epithelium and plays an important role in dipeptide and tripeptide absorption from protein digestion. In this study, we cloned and characterized the cDNA sequence of Janus kinase 2 (JAK2) from Ctenopharyngodon idella. The expression patterns of JAK2 in various tissues and developmental stages were characterized by quantitative real-time PCR (qRT-PCR). The mRNA expression levels of JAK2 and Pept1 regulated by leptin in the intestine were also analyzed in vitro and in vivo. The cDNA sequence of JAK2 is 3378 bp in length, and the mRNA of JAK2 was broadly expressed in all tissues and embryonic stages of C. idella analyzed. In addition, we found that leptin regulated expression of JAK2 and Pept1 in the intestine; Pept1 expression was down-regulated by the JAK2 inhibitor AG490 in vivo and in vitro. Furthermore, luciferase experiments showed that overexpression of the JAK2 gene significantly upregulated the activity of the Pept1 5 regulatory sequence in C. idella. In conclusion, these results may help in elucidating the regulatory effect of the leptin-mediated JAK2 pathway on intestinal Pept1 expression in C. idella and the molecular mechanism of peptide transport by the intestinal transporter Pept1 in fishes.

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Nuclear localization of lymphocyte-specific protein tyrosine kinase (Lck) and its role in regulating LIM domain only 2 (Lmo2) gene

Cited by 18 publications

References 25 publications

Upregulation of Peptide Transporters PEPT1 and PEPT2 by Janus Kinase JAK2

Upregulation of Peptide Transporters PEPT1 and PEPT2 by Janus Kinase JAK2

Nuclear lymphocyte-specific protein tyrosine kinase and its interaction with CR6-interacting factor 1 promote the survival of human leukemic T cells

JAK2 Mediates the Regulation of Pept1 Expression by Leptin in the Grass Carp (Ctenopharyngodon idella) Intestine

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