Mammalian Sterile20-like kinase 1 and the regulation of apoptosis

2004 ◽  
Vol 32 (3) ◽  
pp. 485-488 ◽  
Author(s):  
P.M. de Souza ◽  
M.A. Lindsay
Keyword(s):  
Protein Kinase ◽  
Physiological Function ◽  
Mitogen Activated Protein Kinase ◽  
Serine Threonine Kinase ◽  
Mapk Kinase ◽  
Threonine Kinase ◽  
Abundant Evidence ◽  
Mitogen Activated Protein ◽  
Kinase Pathway

Mammalian Sterile20-like kinase 1 (Mst1) is a ubiquitously expressed serine/threonine kinase which represents a member of the rapidly expanding family of enzymes related to the yeast Sterile20 kinase. Although the physiological function of Mst1 and its role in intracellular signalling is still unclear, reports to date suggest that Mst1, similar to its yeast homologue, operates in the MAPK (mitogen-activated protein kinase) pathway and, in this capacity, may represent a putative MAPK kinase kinase kinase. Moreover, there is abundant evidence for a role of this enzyme in apoptosis, where not only is it a target for caspases, but may also serve as an activator of these proteases to amplify the apoptotic signalling pathway. This paper reviews the investigations that have led to our current understanding of the mechanisms by which Mst1 may be activated and thereby contribute to apoptosis.

scholarly journals Multiple Mitogen-Activated Protein Kinase Signaling Pathways Connect the Cot Oncoprotein to the c-junPromoter and to Cellular Transformation

2000 ◽  
Vol 20 (5) ◽  
pp. 1747-1758 ◽  
Author(s):  
Mario Chiariello ◽  
Maria Julia Marinissen ◽  
J. Silvio Gutkind
Keyword(s):  
Protein Kinase ◽  
Molecular Mechanisms ◽  
Cellular Transformation ◽  
Mitogen Activated Protein Kinase ◽  
Serine Threonine Kinase ◽  
Activated T Cells ◽  
Mapk Kinase ◽  
Threonine Kinase ◽  
Mitogen Activated Protein

ABSTRACT The serine/threonine kinase Cot is a member of the mitogen-activated protein kinase (MAPK) kinase kinase family implicated in cellular transformation. Enhanced expression of this protein has been shown to activate both the MAPK and the c-Jun N-terminal kinase (JNK) pathways and to stimulate the nuclear factor of activated T cells and NF-κB-dependent transcription. However, the nature of the normal functions of the Cot protein and the molecular mechanisms responsible for its oncogenic potential are still largely unknown. Here, we show that overexpression of the cot proto-oncogene is sufficient to stimulate the expression of c-jun and that, in turn, the activity of c-Jun is required for Cot-induced transformation. These observations prompted us to explore the molecular events by which Cot regulates c-jun expression. We found that Cot potently stimulates the activity of the c-jun promoter utilizing JNK-dependent and -independent pathways, the latter involving two novel members of the MAPK family, p38γ (ERK6) and ERK5. Molecularly, this activity was found to be dependent on the ability of Cot to activate, in vivo, members of each class of the MAPK kinase superfamily, including MEK, SEK, MKK6, and MEK5. Furthermore, the use of dominant interfering molecules revealed that Cot requires JNK, p38s, and ERK5 to stimulate the c-jun promoter fully and to induce neoplastic transformation. These findings indicate that Cot represents the first example of a serine/threonine kinase acting simultaneously on all known MAPK cascades. Moreover, these observations strongly suggest that the transforming ability of Cot results from the coordinated activation of these pathways, which ultimately converge on the regulation of the expression and activity of the product of the c-junproto-oncogene.

scholarly journals Sti1 and Cdc37 Can Stabilize Hsp90 in Chaperone Complexes with a Protein Kinase

2004 ◽  
Vol 15 (4) ◽  
pp. 1785-1792 ◽  
Author(s):  
Paul Lee ◽  
Arsalan Shabbir ◽  
Christopher Cardozo ◽  
Avrom J. Caplan
Keyword(s):  
Protein Kinase ◽  
Kinase Domain ◽  
Mitogen Activated Protein Kinase ◽  
Protein Kinase Domain ◽  
Relative Contribution ◽  
Expression Studies ◽  
Mitogen Activated Protein ◽  
Gene Expression Studies ◽  
Kinase Pathway

Hsp90 functions in association with several cochaperones for folding of protein kinases and transcription factors, although the relative contribution of each to the overall reaction is unknown. We assayed the role of nine different cochaperones in the activation of Ste11, a Saccharomyces cerevisiae mitogen-activated protein kinase kinase kinase. Studies on signaling via this protein kinase pathway was measured by α-factor-stimulated induction of FIG1 or lacZ, and repression of HHF1. Several cochaperone mutants tested had reduced FIG1 induction or HHF1 repression, although to differing extents. The greatest defects were in cpr7Δ, sse1Δ, and ydj1Δ mutants. Assays of Ste11 kinase activity revealed a pattern of defects in the cochaperone mutant strains that were similar to the gene expression studies. Overexpression of CDC37, a chaperone required for protein kinase folding, suppressed defects the sti1Δ mutant back to wild-type levels. CDC37 overexpression also restored stable Hsp90 binding to the Ste11 protein kinase domain in the sti1Δ mutant strain. These data suggest that Cdc37 and Sti1 have functional overlap in stabilizing Hsp90:client complexes. Finally, we show that Cns1 functions in MAP kinase signaling in association with Cpr7.

Role of mitogen-activated protein kinase pathway in acetylcholine-mediated in vitro relaxation of rat pulmonary artery

2002 ◽  
Vol 434 (1-2) ◽  
pp. 55-64 ◽  
Author(s):  
Wai Yee Choy ◽  
Yung Fat Wong ◽  
Yiu Wa Kwan ◽  
Alice Lai Shan Au ◽  
Wing Hung Lau ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Pulmonary Artery ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Kinase Pathway
Sign in / Sign up

Export Citation Format

Share Document