Biochemical Analysis of MST1 Kinase: Elucidation of a C-Terminal Regulatory Region

Anand, Ruchi; Kim, Ah-Young; Brent, Michael; Marmorstein, Ronen

doi:10.1021/bi800309m

Cited by 42 publications

(50 citation statements)

References 33 publications

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“…The K m values for MYO3A were about 100-fold lower than the reported values for PAK1 determined with a peptide substrate (40). The steady state kinetic parameters (k cat and K m ) determined for other kinases vary considerably, although the values for MYO3A are similar to those reported for mammalian target of rapamycin (44) and MST1 (45). Many kinases are auto-inhibited by the C-or N-terminal domains and utilize protein-protein interactions to relieve autoinhibition (17).…”

Section: Discussionsupporting

confidence: 43%

Myosin 3A Kinase Activity Is Regulated by Phosphorylation of the Kinase Domain Activation Loop

Quintero

Unrath

Stevens

et al. 2013

Journal of Biological Chemistry

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Background: Class III myosins contain both a motor and kinase domain. Results: Phosphorylation of the kinase activation loop enhances MYO3A kinase activity, augmenting autophosphorylationinduced attenuation of motor and cellular activity. Conclusion: MYO3A kinase activity mediates localization and function within actin protrusions. Significance: Characterizing MYO3A kinase regulation enhances our understanding of the role of MYO3A in the maintenance of actin protrusions found in sensory epithelia.

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Section: Discussionsupporting

confidence: 43%

Myosin 3A Kinase Activity Is Regulated by Phosphorylation of the Kinase Domain Activation Loop

Quintero

Unrath

Stevens

et al. 2013

Journal of Biological Chemistry

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“…Recent evidence suggests that the C-terminal domain of MST1 is versatile and can exhibit stimulatory activity, depending on the specific substrate (Anand et al, 2008). The SARAH domain has been shown to be critical for the interaction of MST1 and its interacting proteins, such as the WW45 and RASSF family proteins (Zeng and Hong, 2008).…”

mentioning

confidence: 99%

The c-Abl-MST1 Signaling Pathway Mediates Oxidative Stress-Induced Neuronal Cell Death

Xiao¹,

Chen²,

Hu³

et al. 2011

Journal of Neuroscience

110

102

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Oxidative stress influences cell survival and homeostasis, but the mechanisms underlying the biological effects of oxidative stress remain to be elucidated. The protein kinase MST1 (mammalian Ste20-like kinase 1) plays a major role in oxidative stress-induced cell death in primary mammalian neurons. However, the mechanisms that regulate MST1 in oxidative stress responses remain largely unknown. In the present study, we demonstrate that the protein kinase c-Abl phosphorylates MST1 at Y433, which triggers the stabilization and activation of MST1.

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“…3C). It has been reported that the C-terminal region of MST1 participates in protein dimerization and mediates MST1 activation onto the substrates, such as FOXO1 (22). We sought to examine whether Ser-82 phosphorylation might affect its homodimerization.…”

Section: Jnk Interacts With Mst1 and Activates Mst1 Kinase Activity Imentioning

confidence: 99%

c-Jun N-terminal Kinase Enhances MST1-mediated Pro-apoptotic Signaling through Phosphorylation at Serine 82

Xiao

Jia

et al. 2010

Journal of Biological Chemistry

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Protein kinases play an important role in the maintenance of homeostasis between cell survival and apoptosis. Deregulation of these kinases leads to various pathological manifestations, such as cancer and neurodegenerative diseases. The MST1 encodes a serine/threonine kinase that is activated upon apoptotic stimulation, which in turn phosphorylates its downstream targets, Histone H2B and FOXO. However, the upstream regulators of MST1 kinase have been poorly studied. In this study, we report that JNK (c-Jun N-terminal kinase) phosphorylates MST1 at serine 82, which leads to the enhancement of MST1activation.Accordingly,theactivationofMST1phosphor-ylates FOXO3 at serine 207 and promotes cell death. The inhibition of JNK kinase per se attenuates MST1 activity and nuclear translocation as well as MST1-induced apoptosis. We also find the S82A (serine mutated to alanine) diminishes MST1 activation and its effect on the FOXO transcription activity. Collectively, these findings define the novel feedback regulation of MST1 kinase activation by its putative substrate, JNK, with implication for our understanding of the signaling mechanism during cell death.Mammalian sterile 20-like kinase 1 (MST1), 4 a mammalian homolog of Drosophila Hippo, contains a Ste20-related kinase catalytic domain in the N-terminal region and a regulatory domain at the C terminus (1). In Drosophila, recent studies showed that Hippo restricts cell growth and cell proliferation and promotes cell death by interacting with Salvador (Sav) and Warts (Wts), which result in inhibition of transcription and/or degradation of cyclin E and DIAPs (2, 3) through phosphorylating Yorkie (4). The non-catalytic tail of MST1 has been shown to be cleaved by caspase-3 upon various apoptotic stimuli such as death receptor triggering by CD95/FasL and treatments with staurosporine (STS), ceramide, as well as heat shock and arsenite. The N terminus of MST1 translocates to the nucleus, where it promotes chromatin condensation and herein apoptosis (5-7). In addition, MST1 cleavage and induced apoptosis were also observed upon overexpression (8). Asp-326 and Asp-349 has been reported to be the two major cleavage sites, and the mutation of the cleavage sites attenuates its kinase activation, nuclear translocation, and ability to induce apoptosis (7, 9). In mammals, it has been shown that MST1 apparently activates JNK and p38MAPK kinase pathways through MKK4/ MKK7 and MKK3/MKK6, respectively (6). Recently it was reported that activation of the JNK kinase pathway is essential and sufficient for MST1-mediated chromatin condensation and apoptosis (10), and the dominant-negative mutant of JNK, not dominant-negative p38 or the p38 inhibitor inhibited MST1-induced caspase activation and cell death (11).Recently, the Allis group (8, 12) reported that MST1 induces apoptosis by phosphorylating histone H2B on a conserved site, serine 14 in mammalian cells and serine 10 in Saccharomyces cerevisiae. MST1 has also been implicated in the control of neuronal cell death via phosphorylating FOX...

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Biochemical Analysis of MST1 Kinase: Elucidation of a C-Terminal Regulatory Region

Cited by 42 publications

References 33 publications

Myosin 3A Kinase Activity Is Regulated by Phosphorylation of the Kinase Domain Activation Loop

Myosin 3A Kinase Activity Is Regulated by Phosphorylation of the Kinase Domain Activation Loop

The c-Abl-MST1 Signaling Pathway Mediates Oxidative Stress-Induced Neuronal Cell Death

c-Jun N-terminal Kinase Enhances MST1-mediated Pro-apoptotic Signaling through Phosphorylation at Serine 82

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