APPARENT ADENYLATE KINASE ACTIVITY IN VIVO

Abstract In response to changing light quantity and quality, photosynthetic organisms perform state transitions, a process which optimizes photosynthetic yield and mitigates photo-damage. The serine/threonine-protein kinase STN7 phosphorylates the light-harvesting complex of photosystem II (PSII; light-harvesting complex II), which then migrates from PSII to photosystem I (PSI), thereby rebalancing the light excitation energy between the photosystems and restoring the redox poise of the photosynthetic electron transport chain. Two conserved cysteines forming intra- or intermolecular disulfide bonds in the lumenal domain (LD) of STN7 are essential for the kinase activity although it is still unknown how activation of the kinase is regulated. In this study, we show lumen thiol oxidoreductase 1 (LTO1) is co-expressed with STN7 in Arabidopsis (Arabidopsis thaliana) and interacts with the LD of STN7 in vitro and in vivo. LTO1 contains thioredoxin (TRX)-like and vitamin K epoxide reductase domains which are related to the disulfide-bond formation system in bacteria. We further show that the TRX-like domain of LTO1 is able to oxidize the conserved lumenal cysteines of STN7 in vitro. In addition, loss of LTO1 affects the kinase activity of STN7 in Arabidopsis. Based on these results, we propose that LTO1 helps to maintain STN7 in an oxidized active state in state 2 through redox interactions between the lumenal cysteines of STN7 and LTO1.

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Acidic and basic fibroblast growth factors stimulate tyrosine kinase activity in vivo.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(19)35450-x ◽

1988 ◽

Vol 263 (2) ◽

pp. 988-993 ◽

Cited By ~ 4

Author(s):

S R Coughlin ◽

P J Barr ◽

L S Cousens ◽

L J Fretto ◽

L T Williams

Keyword(s):

Growth Factors ◽

Tyrosine Kinase ◽

Kinase Activity ◽

Fibroblast Growth Factors ◽

Fibroblast Growth ◽

Tyrosine Kinase Activity

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Essential role of IRAK-4 protein and its kinase activity in Toll-like receptor–mediated immune responses but not in TCR signaling

Journal of Experimental Medicine ◽

10.1084/jem.20061523 ◽

2007 ◽

Vol 204 (5) ◽

pp. 1013-1024 ◽

Cited By ~ 120

Author(s):

Tatsukata Kawagoe ◽

Shintaro Sato ◽

Andreas Jung ◽

Masahiro Yamamoto ◽

Kosuke Matsui ◽

...

Keyword(s):

Immune Responses ◽

Kinase Activity ◽

Interleukin 1 ◽

Cell Receptor ◽

Nuclear Factor Κb ◽

Toll Like Receptor ◽

Tcr Signaling ◽

Mitogen Activated Protein

Interleukin-1 receptor–associated kinase 4 (IRAK-4) was reported to be essential for the Toll-like receptor (TLR)– and T cell receptor (TCR)–mediated signaling leading to the activation of nuclear factor κB (NF-κB). However, the importance of kinase activity of IRAK family members is unclear. In this study, we investigated the functional role of IRAK-4 activity in vivo by generating mice carrying a knockin mutation (KK213AA) that abrogates its kinase activity. IRAK-4KN/KN mice were highly resistant to TLR-induced shock response. The cytokine production in response to TLR ligands was severely impaired in IRAK-4KN/KN as well as IRAK-4−/− macrophages. The IRAK-4 activity was essential for the activation of signaling pathways leading to mitogen-activated protein kinases. TLR-induced IRAK-4/IRAK-1–dependent and –independent pathways were involved in early induction of NF-κB–regulated genes in response to TLR ligands such as tumor necrosis factor α and IκBζ. In contrast to a previous paper (Suzuki, N., S. Suzuki, D.G. Millar, M. Unno, H. Hara, T. Calzascia, S. Yamasaki, T. Yokosuka, N.J. Chen, A.R. Elford, et al. 2006. Science. 311:1927–1932), the TCR signaling was not impaired in IRAK-4−/− and IRAK-4KN/KN mice. Thus, the kinase activity of IRAK-4 is essential for the regulation of TLR-mediated innate immune responses.

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Nano‐mediator‐effector cascade systems for amplified protein kinase activity imaging and phosphorylation‐induced drug release in vivo

Angewandte Chemie ◽

10.1002/ange.202109108 ◽

2021 ◽

Author(s):

Fenfen Zheng ◽

Tiantian Meng ◽

Difei Jiang ◽

Jiamin Sun ◽

Haiyang Yao ◽

...

Keyword(s):

Protein Kinase ◽

Drug Release ◽

Kinase Activity ◽

Protein Kinase Activity ◽

Cascade Systems

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Autophosphorylation of DNA-PKCS regulates its dynamics at DNA double-strand breaks

The Journal of Cell Biology ◽

10.1083/jcb.200608077 ◽

2007 ◽

Vol 177 (2) ◽

pp. 219-229 ◽

Cited By ~ 256

Author(s):

Naoya Uematsu ◽

Eric Weterings ◽

Ken-ichi Yano ◽

Keiko Morotomi-Yano ◽

Burkhard Jakob ◽

...

Keyword(s):

Kinase Activity ◽

Laser System ◽

Double Strand Breaks ◽

Dependent Manner ◽

Dna Double Strand Breaks ◽

End Joining ◽

Dsb Repair ◽

Strand Breaks ◽

Dna Ends

The DNA-dependent protein kinase catalytic subunit (DNA-PKCS) plays an important role during the repair of DNA double-strand breaks (DSBs). It is recruited to DNA ends in the early stages of the nonhomologous end-joining (NHEJ) process, which mediates DSB repair. To study DNA-PKCS recruitment in vivo, we used a laser system to introduce DSBs in a specified region of the cell nucleus. We show that DNA-PKCS accumulates at DSB sites in a Ku80-dependent manner, and that neither the kinase activity nor the phosphorylation status of DNA-PKCS influences its initial accumulation. However, impairment of both of these functions results in deficient DSB repair and the maintained presence of DNA-PKCS at unrepaired DSBs. The use of photobleaching techniques allowed us to determine that the kinase activity and phosphorylation status of DNA-PKCS influence the stability of its binding to DNA ends. We suggest a model in which DNA-PKCS phosphorylation/autophosphorylation facilitates NHEJ by destabilizing the interaction of DNA-PKCS with the DNA ends.

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Role for the Ran Binding Protein, Mog1p, in Saccharomyces cerevisiae SLN1-SKN7 Signal Transduction

Eukaryotic Cell ◽

10.1128/ec.3.6.1544-1556.2004 ◽

2004 ◽

Vol 3 (6) ◽

pp. 1544-1556 ◽

Cited By ~ 17

Author(s):

Jade Mei-Yeh Lu ◽

Robert J. Deschenes ◽

Jan S. Fassler

Keyword(s):

Signal Transduction ◽

Transcription Factor ◽

Osmotic Stress ◽

Kinase Activity ◽

Mitogen Activated Protein Kinase ◽

Osmotic Response ◽

Mitogen Activated Protein ◽

Kinase Pathway

ABSTRACT Yeast Sln1p is an osmotic stress sensor with histidine kinase activity. Modulation of Sln1 kinase activity in response to changes in the osmotic environment regulates the activity of the osmotic response mitogen-activated protein kinase pathway and the activity of the Skn7p transcription factor, both important for adaptation to changing osmotic stress conditions. Many aspects of Sln1 function, such as how kinase activity is regulated to allow a rapid response to the continually changing osmotic environment, are not understood. To gain insight into Sln1p function, we conducted a two-hybrid screen to identify interactors. Mog1p, a protein that interacts with the yeast Ran1 homolog, Gsp1p, was identified in this screen. The interaction with Mog1p was characterized in vitro, and its importance was assessed in vivo. mog1 mutants exhibit defects in SLN1-SKN7 signal transduction and mislocalization of the Skn7p transcription factor. The requirement for Mog1p in normal localization of Skn7p to the nucleus does not fully account for the mog1-related defects in SLN1-SKN7 signal transduction, raising the possibility that Mog1p may play a role in Skn7 binding and activation of osmotic response genes.

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Mice Lacking the Inhibitory Collagen Receptor LAIR-1 Exhibit a Mild Thrombocytosis and Hyperactive Platelets

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.117.309253 ◽

2017 ◽

Vol 37 (5) ◽

pp. 823-835 ◽

Cited By ~ 18

Author(s):

Christopher W. Smith ◽

Steven G. Thomas ◽

Zaher Raslan ◽

Pushpa Patel ◽

Maxwell Byrne ◽

...

Keyword(s):

Tyrosine Kinases ◽

Kinase Activity ◽

Thrombus Formation ◽

Physiological Role ◽

Src Family Kinase ◽

Glycoprotein Vi ◽

Collagen Receptor ◽

Deficient Mice

Objective— Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is a collagen receptor that belongs to the inhibitory immunoreceptor tyrosine-based inhibition motif–containing receptor family. It is an inhibitor of signaling via the immunoreceptor tyrosine-based activation motif–containing collagen receptor complex, glycoprotein VI-FcRγ-chain. It is expressed on hematopoietic cells, including immature megakaryocytes, but is not detectable on platelets. Although the inhibitory function of LAIR-1 has been described in leukocytes, its physiological role in megakaryocytes and in particular in platelet formation has not been explored. In this study, we investigate the role of LAIR-1 in megakaryocyte development and platelet production by generating LAIR-1–deficient mice. Approach and Results— Mice lacking LAIR-1 exhibit a significant increase in platelet counts, a prolonged platelet half-life in vivo, and increased proplatelet formation in vitro. Interestingly, platelets from LAIR-1–deficient mice exhibit an enhanced reactivity to collagen and the glycoprotein VI–specific agonist collagen-related peptide despite not expressing LAIR-1, and mice showed enhanced thrombus formation in the carotid artery after ferric chloride injury. Targeted deletion of LAIR-1 in mice results in an increase in signaling downstream of the glycoprotein VI–FcRγ-chain and integrin αIIbβ3 in megakaryocytes because of enhanced Src family kinase activity. Conclusions— Findings from this study demonstrate that ablation of LAIR-1 in megakaryocytes leads to increased Src family kinase activity and downstream signaling in response to collagen that is transmitted to platelets, rendering them hyper-reactive specifically to agonists that signal through Syk tyrosine kinases, but not to G-protein–coupled receptors.

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Viral dosing of influenza A infection reveals involvement of RIPK3 and FADD, but not MLKL

Cell Death and Disease ◽

10.1038/s41419-021-03746-0 ◽

2021 ◽

Vol 12 (5) ◽

Author(s):

Teodora Oltean ◽

Emily Van San ◽

Tatyana Divert ◽

Tom Vanden Berghe ◽

Xavier Saelens ◽

...

Keyword(s):

Influenza A Virus ◽

Influenza A ◽

Kinase Activity ◽

Dose Range ◽

Challenge Dose

AbstractRIPK3 was reported to play an important role in the protection against influenza A virus (IAV) in vivo. Here we show that the requirement of RIPK3 for protection against IAV infection in vivo is only apparent within a limited dose range of IAV challenge. We found that this protective outcome is independent from RIPK3 kinase activity and from MLKL. This shows that platform function of RIPK3 rather than its kinase activity is required for protection, suggesting that a RIPK3 function independent of necroptosis is implicated. In line with this finding, we show that FADD-dependent apoptosis has a crucial additional effect in protection against IAV infection. Altogether, we show that RIPK3 contributes to protection against IAV in a narrow challenge dose range by a mechanism that is independent of its kinase activity and its capacity to induce necroptosis.

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Activation of c-Src in cells bearing v-Crk and its suppression by Csk

Molecular and Cellular Biology ◽

10.1128/mcb.12.10.4706-4713.1992 ◽

1992 ◽

Vol 12 (10) ◽

pp. 4706-4713

Author(s):

H Sabe ◽

M Okada ◽

H Nakagawa ◽

H Hanafusa

Keyword(s):

Tyrosine Kinase ◽

Tyrosine Phosphorylation ◽

Protein Tyrosine Kinase ◽

Kinase Activity ◽

Src Kinase ◽

Cellular Protein ◽

Morphological Transformation ◽

Protein Tyrosine ◽

In Cells

The protein product of the CT10 virus, p47gag-crk (v-Crk), which contains Src homology region 2 (SH2) and 3 (SH3) domains but lacks a kinase domain, is believed to cause an increase in cellular protein tyrosine phosphorylation. A candidate tyrosine kinase, Csk (C-terminal Src kinase), has been implicated in c-Src Tyr-527 phosphorylation, which negatively regulates the protein tyrosine kinase of pp60c-src (c-Src). To investigate how c-Src kinase activity is regulated in vivo, we first looked at whether v-Crk can activate c-Src kinase. We found that cooverexpression of v-Crk and c-Src caused elevation of c-Src kinase activity, resulting in an increase of tyrosine phosphorylation of cellular proteins and morphological transformation of rat 3Y1 fibroblasts. v-Crk and c-Src complexes were not detected, although v-Crk bound to a variety of tyrosine-phosphorylated proteins in cells overexpressing v-Crk and c-Src. Overexpression of Csk in these transformed cells caused reversion to normal phenotypes and also reduced the level of c-Src kinase activity. However, Csk did not cause reversion of cells transformed by v-Src or c-Src527F, in which Tyr-527 was changed to Phe. These results strongly suggest that Csk acts on Tyr-527 of c-Src and suppresses c-Src kinase activity in vivo. Because Csk can suppress transformation by cooverexpression of v-Crk and c-Src, we suggest that v-Crk causes activation of c-Src in vivo by altering the phosphorylation state of Tyr-527.

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Functional domains of the pp60v-src protein as revealed by analysis of temperature-sensitive Rous sarcoma virus mutants

Molecular and Cellular Biology ◽

10.1128/mcb.4.8.1508-1514.1984 ◽

1984 ◽

Vol 4 (8) ◽

pp. 1508-1514

Author(s):

A W Stoker ◽

P J Enrietto ◽

J A Wyke

Keyword(s):

Rous Sarcoma Virus ◽

Kinase Activity ◽

Temperature Sensitive ◽

Tyrosine Kinase Activity ◽

Rous Sarcoma ◽

Heat Labile ◽

Src Gene ◽

Sarcoma Virus

Four temperature-sensitive (ts) Rous sarcoma virus src gene mutants with lesions in different parts of the gene represent three classes of alteration in pp60src. These classes are composed of mutants with (i) heat-labile protein kinase activities both in vitro and in vivo (tsLA27 and tsLA29), (ii) heat-labile kinases in vivo but not in vitro (tsLA33), and (iii) neither in vivo nor in vitro heat-labile kinases (tsLA32). The latter class indicates the existence of structural or functional pp60src domains that are required for transformation but do not grossly affect tyrosine kinase activity.

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