Activation of the MKK4‐JNK pathway during erythroid differentiation of K562 cells is inhibited by the heat shock factor 2‐β isoform

Hietakangas, Ville; Elo, Iina; Rosenström, Heidi; Coffey, Eleanor T.; Kyriakis, John; Eriksson, John E.; Sistonen, Lea

doi:10.1016/s0014-5793(01)02810-1

Cited by 8 publications

(6 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, our studies provided the first evidence demonstrating that MKK4 but not MKK7 was a major upstream activator of JNK during RA‐induced endodermal differentiation of P19 cells. In this context it should be noted that Hietakangas and coworkers showed that activation of JNK during hematopoietic differentiation of K562 cells was also mediated through activation of MKK4 but not MKK7 [10].…”

Section: Resultsmentioning

confidence: 99%

Activation mechanism of c‐Jun amino‐terminal kinase in the course of endodermal differentiation of P19 embryonic carcinoma cells

Kudo¹,

Sakamoto²,

Tamura³

et al. 2003

FEBS Letters

View full text Add to dashboard Cite

c-Jun amino-terminal kinase (JNK) is known to be activated and play critical roles during neural and endodermal di¡erentiation of P19 embryonic carcinoma cells. In this study we demonstrated that of the two upstream protein kinases of JNK, only MKK4 activity was substantially enhanced in the endodermally di¡erentiating P19 cells. This enhanced activity of MKK4 stemmed from the increased expression of MKK4 and its activation by phosphorylation. Activated MKK4 and JNK were localized in both nucleus and cytoplasm of the di¡er-entiating cells, while they were localized only in the nucleus in the undi¡erentiated cells, suggesting multiple roles of JNK in the course of the endodermal di¡erentiation of P19 cells.

show abstract

Section: Resultsmentioning

confidence: 99%

Activation mechanism of c‐Jun amino‐terminal kinase in the course of endodermal differentiation of P19 embryonic carcinoma cells

Kudo¹,

Sakamoto²,

Tamura³

et al. 2003

FEBS Letters

View full text Add to dashboard Cite

show abstract

“…2002) is the sole mechanism involved in suppressing glutamate‐induced JNK and p38 activation. It has been reported that heat shock protein (HSP) and its transcriptional regulator, heat shock factor (HSF), inactivate JNK presumably through HSF‐induced inhibition of the upstream MKK4 (Hietakangas et al . 2001), HSP‐mediated enhancement of JNK dephosphorylation (Gabai et al .…”

Section: Discussionmentioning

confidence: 99%

Regulation of c‐Jun N‐terminal kinase, p38 kinase and AP‐1 DNA binding in cultured brain neurons: roles in glutamate excitotoxicity and lithium neuroprotection

Chen

Qin

Ren

et al. 2003

Journal of Neurochemistry

141

View full text Add to dashboard Cite

In rat cerebellar granule cells, glutamate induced rapid activation of c-Jun N-terminal kinase (JNK) and p38 kinase to phosphorylate c-Jun (at Ser63) and p53 (at Ser15), respectively, and a subsequent marked increase in activator protein-1 (AP-1) binding that preceded apoptotic death. These glutamate-induced effects and apoptosis could largely be prevented by long-term (7 days) pretreatment with 0.5-2 mM lithium, an antibipolar drug. Glutamate's actions could also be prevented by known blockers of this pathway, MK-801 (an NMDA receptor blocker), SB 203580 (a p38 kinase inhibitor) and curcumin (an AP-1 binding inhibitor). The concentration-and time-dependent suppression of glutamate's effects by lithium and curcumin correlated well with their neuroprotective effects. These results suggest a prominent role of JNK and p38, as well as their downstream AP-1 binding activation and p53 phosphorylation in mediating glutamate excitotoxicity. Moreover, the neuroprotective effects of lithium are mediated, at least in part, by suppressing NMDA receptor-mediated activation of the mitogen-activated protein kinase pathway.

show abstract

“…Several pathways including JAK-STAT signaling pathway and MKK4-JNK have been implicated in drug and the heat shock factor 2-b-mediated erythrocyte differentiation and the production of hemoglobin in erythroid progenitors. [38][39][40] . Thus, SB220025 or SB203580, at a concentration of 10 mM, may also concurrently inhibit other events required for erythrocyte differentiation and the production of hemoglobin.…”

Section: Discussionmentioning

confidence: 99%

CPEC induces erythroid differentiation of human myeloid leukemia K562 cells through CTP depletion and p38 MAP kinase

et al. 2004

View full text Add to dashboard Cite

Cyclopentenyl cytosine (CPEC) is a carbocyclic cytidine analog inhibitor of CTP synthetase and experimental drug for combination chemotherapy. CPEC treatment (50 nM) depleted intracellular CTP and induced a specific S-phase arrest and erythroid differentiation of human erythroleukemia K562 cells. The equilibrative nucleoside transporters (ENT1, 2) facilitated uptake of CPEC into K562 cells as evidenced by both NBMPR and dipyridamole inhibition of CPEC-mediated CTP depletion and erythroid differentiation. Incubation with the pyridinylimidazole p38 MAPK inhibitors, SB203580 or SB220025, suppressed both the CPEC-induced cell cycle arrest and differentiation of K562 cells. SB203580 also prevented the cell cycle arrest and erythroid differentiation of K562 cells induced by Leflunomide (LEF), a non-nucleoside inhibitor of the de novo pyrimidine pathway, without affecting LEF-induced depletion of pyrimidine pools. Finally, selective knockdown of p38 MAPK by using Smart Poolt siRNA to p38 MAPK significantly decreased the CPEC-induced differentiation of K562 cells. These results suggest that endogenous activity of p38 MAP kinases may be required for committing K562 cells to cell cycle arrest and erythroid differentiation under conditions of CTP depletion.

show abstract

Activation of the MKK4‐JNK pathway during erythroid differentiation of K562 cells is inhibited by the heat shock factor 2‐β isoform

Cited by 8 publications

References 28 publications

Activation mechanism of c‐Jun amino‐terminal kinase in the course of endodermal differentiation of P19 embryonic carcinoma cells

Activation mechanism of c‐Jun amino‐terminal kinase in the course of endodermal differentiation of P19 embryonic carcinoma cells

Regulation of c‐Jun N‐terminal kinase, p38 kinase and AP‐1 DNA binding in cultured brain neurons: roles in glutamate excitotoxicity and lithium neuroprotection

CPEC induces erythroid differentiation of human myeloid leukemia K562 cells through CTP depletion and p38 MAP kinase

Contact Info

Product

Resources

About