Highly synchronous culture of fibroblasts from G2 block caused by staurosporine, a potent inhibitor of protein kinases

Stress-activated MAPKs (SAPKs) respond to a wide variety of stressors. In most cases, the pathways through which specific stress signals are transmitted to the SAPKs are not known. In this study, we delineate the intracellular signaling pathway by which the trivalent toxic metalloid arsenite [As(III)] activates the yeast SAPK Hog1. We demonstrate that, to activate Hog1, As(III) must enter the cell through the glycerol channel Fps1 and must be metabolized to methyl arsenite [MAs(III)] by the dimeric methyltransferase Mtq2:Trm112. We found that Mtq2:Trm1 displays SAM-dependent methyltransferase activity toward both As(III) and MAs(III). Additionally, we present genetic and biochemical evidence that MAs(III), but not As(III), is a potent inhibitor of the protein tyrosine phosphatases (Ptp2 and Ptp3) that normally maintain Hog1 in an inactive state. Inhibition of Ptp2 and Ptp3 by MAs(III) results in elevated Hog1 phosphorylation without activation of the protein kinases that act upstream of the SAPK and raises the possibility that other Hog1-activating stressors act intracellularly at different points along the canonical Hog1 activation pathway. Finally, we show that arsenate [As(V)], a pentavalent form of arsenic, also activates Hog1, but through a pathway that is distinct from that of As(III) and involves activation of the Hog1 MEK Pbs2.

Download Full-text

K252a, a potent inhibitor of protein kinases, inhibits the migration of cerebellar granule cells in vitro

Developmental Brain Research ◽

10.1016/0165-3806(96)83492-4 ◽

1995 ◽

Vol 90 (1-2) ◽

pp. 122-128 ◽

Cited By ~ 4

Author(s):

Satoshi Kobayashi ◽

Kaoru Isa ◽

Kensuke Hayashi ◽

Hiroshi K. Inoue ◽

Keiichi Uyemura ◽

...

Keyword(s):

Protein Kinases ◽

Granule Cells ◽

Cerebellar Granule Cells ◽

Potent Inhibitor ◽

Cerebellar Granule

Download Full-text

1-(5-isoquinolinesulfonyl)-2-methylpiperazine(H-7), a potent inhibitor of protein kinases, inhibits the differentiation of HL-60 cells induced by phorbol diester

Life Sciences ◽

10.1016/0024-3205(86)90202-x ◽

1986 ◽

Vol 39 (12) ◽

pp. 1101-1107 ◽

Cited By ~ 32

Author(s):

Masakatsu Nishikawa ◽

Yasuhiro Uemura ◽

Hiroyoshi Hidaka ◽

Shigeru Shirakawa

Keyword(s):

Protein Kinases ◽

Potent Inhibitor

Download Full-text

A Novel Pyrazolo[1,5-a]pyrimidine Is a Potent Inhibitor of Cyclin-Dependent Protein Kinases 1, 2, and 9, Which Demonstrates Antitumor Effects in Human Tumor Xenografts Following Oral Administration

Journal of Medicinal Chemistry ◽

10.1021/jm100732t ◽

2010 ◽

Vol 53 (24) ◽

pp. 8508-8522 ◽

Cited By ~ 46

Author(s):

Dean A. Heathcote ◽

Hetal Patel ◽

Sebastian H. B. Kroll ◽

Pascale Hazel ◽

Manikandan Periyasamy ◽

...

Keyword(s):

Oral Administration ◽

Protein Kinases ◽

Potent Inhibitor ◽

Human Tumor ◽

Antitumor Effects ◽

Human Tumor Xenografts ◽

Tumor Xenografts ◽

Dependent Protein

Download Full-text

An efficient synthesis of an exo-enone analogue of LL-Z1640-2 and evaluation of its protein kinase inhibitory activities

Organic & Biomolecular Chemistry ◽

10.1039/c5ob01948f ◽

2016 ◽

Vol 14 (2) ◽

pp. 639-645 ◽

Cited By ~ 5

Author(s):

Stephanie Q. Wang ◽

Shermin S. Goh ◽

Christina L. L. Chai ◽

Anqi Chen

Keyword(s):

Protein Kinase ◽

Protein Kinases ◽

Potent Inhibitor ◽

Reductive Coupling ◽

Related Protein ◽

Efficient Synthesis ◽

Inhibitory Activities ◽

Nanomolar Range

An exo-enone analogue of LL-Z1640-2 has been synthesised efficiently using a Ni-catalysed reductive coupling macrocyclisation of an alkyne–aldehyde. The analogue has been shown to be a potent inhibitor of several cancer related protein kinases at the nanomolar range.

Download Full-text