Integrative Transcriptomics and Proteomics Analyses to Reveal the Developmental Regulation of Metorchis orientalis: A Neglected Trematode With Potential Carcinogenic Implications

Metorchis orientalis is a neglected zoonotic parasite of the gallbladder and bile duct of poultry, mammals, and humans. It has been widely reported in Asian, including China, Japanese, and Korea, where it is a potential threat to public health. Despite its significance as an animal and human pathogen, there are few published transcriptomic and proteomics data available. Transcriptome Illumina RNA sequencing and label-free protein quantification were performed to compare the gene and protein expression of adult and metacercariae-stage M. orientalis, resulting in 100,234 unigenes and 3,530 proteins. Of these, 13,823 differentially expressed genes and 1,445 differentially expressed proteins were identified in adult versus metacercariae. In total, 570 genes were differentially expressed consistent with the mRNA and protein level in the adult versus metacercariae stage. Differential gene transcription analyses revealed 34,228 genes to be expressed in both stages, whereas 66,006 genes showed stage-specific expression. Compared with adults, the metacercariae stage was highly transcriptional. GO and KEGG analyses based on transcriptome and proteome revealed numerous up-regulated genes in adult M. orientalis related to microtubule-based processes, microtubule motor activity, and nucleocytoplasmic transport. The up-regulated genes in metacercariae M. orientalis were mainly related to transmembrane receptor protein serine/threonine kinase activity, transmembrane receptor protein serine/threonine kinase signaling pathway. Transcriptome and proteome comparative analyses showed numerous up-regulated genes in adult stage were mainly enriched in actin filament capping, spectrin, and glucose metabolic process, while up-regulated genes in metacercariae stage were mainly related to cilium assembly, cilium movement, and motile cilium. These results highlight changes in protein and gene functions during the development of metacercariae into adults, and provided evidence for the mechanisms involved in morphological and metabolic changes at both the protein and gene levels. Interestingly, many genes had been proved associated with liver fibrosis and carcinogenic factors were identified highly expressed in adult M. orientalis, which suggests that M. orientalis is a neglected trematode with potential carcinogenic implications. These data provide attractive targets for the development of therapeutic or diagnostic interventions for controlling M. orientalis.

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Relevance of STK11 Mutations Regarding Immune Cell Infiltration, Drug Sensitivity, and Cellular Processes in Lung Adenocarcinoma

Frontiers in Oncology ◽

10.3389/fonc.2020.580027 ◽

2020 ◽

Vol 10 ◽

Author(s):

Zhenqing Li ◽

Bo Ding ◽

Jianxun Xu ◽

Kai Mao ◽

Pengfei Zhang ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Drug Sensitivity ◽

Immune Cell ◽

Differentially Expressed ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Wild Type ◽

Serine Threonine Kinase ◽

Threonine Kinase ◽

Cellular Processes

Serine/threonine kinase 11 (STK11) is one member of the serine/threonine kinase family, which is involved in regulating cell polarity, apoptosis, and DNA damage repair. In lung adenocarcinoma (LUAD), it can play as one tumor suppressor and always be mutated. In this study, we aimed to assess the relevance of STK11 mutations in LUAD, in which we also studied the correlation among immune cell infiltration, drug sensitivity, and cellular processes. By performing the bioinformatics analysis of the Cancer Genome Atlas (TCGA) about LUAD patients, we found that the mutation efficiency of STK11 mutations is about 19%. Additionally, the differentially expressed gene analysis showed that there were 746 differentially expressed genes (DEGs) between LUAD patients with and without STK11 mutations. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis showed that the DEGs were enriched in various tumorigenesis signaling pathways and metabolic processes. Among these DEGs, the top ranking 21 genes were found that they were more frequently mutated in the STK11 mutation group than in the wild-type group (p-value<0.01). Finally, the LUAD patients with STK11 mutations suffered the worse immune cell infiltration levels than the LUAD patients with wild-type. The STK11 gene copy number was correlated with immune cell infiltration. Aiming to develop the therapeutic drugs, we performed Genomics of Drug Sensitivity in Cancer (GDSC) data to identify the potential therapeutic candidate and the results showed that Nutlin-3a(-) may be a sensitive drug for LUAD cases harboring STK11 mutations. The specific genes and pathways shown to be associated with LUAD cases involving STK11 mutations may serve as targets for individualized LUAD treatment.

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PknH, a transmembrane Hank's type serine/threonine kinase fromMycobacterium tuberculosisis differentially expressed under stress conditions

FEMS Microbiology Letters ◽

10.1016/j.femsle.2004.01.045 ◽

2004 ◽

Vol 233 (1) ◽

pp. 107-113 ◽

Cited By ~ 25

Author(s):

Kirti Sharma ◽

Harish Chandra ◽

Pradeep K. Gupta ◽

Monika Pathak ◽

Azeet Narayan ◽

...

Keyword(s):

Stress Conditions ◽

Differentially Expressed ◽

Serine Threonine Kinase ◽

Threonine Kinase

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A PERK-Like Receptor Kinase Interacts with the Geminivirus Nuclear Shuttle Protein and Potentiates Viral Infection

Journal of Virology ◽

10.1128/jvi.00173-06 ◽

2006 ◽

Vol 80 (13) ◽

pp. 6648-6656 ◽

Cited By ~ 53

Author(s):

Lilian H. Florentino ◽

Anésia A. Santos ◽

Mariana R. Fontenelle ◽

Guilherme L. Pinheiro ◽

Francisco M. Zerbini ◽

...

Keyword(s):

Intracellular Transport ◽

Kinase Domain ◽

Receptor Protein ◽

Nuclear Shuttle Protein ◽

Serine Threonine Kinase ◽

Viral Dna ◽

Functional Link ◽

Threonine Kinase

ABSTRACT The nuclear shuttle protein (NSP) from bipartite geminiviruses facilitates the intracellular transport of viral DNA from the nucleus to the cytoplasm and acts in concert with the movement protein (MP) to promote the cell-to-cell spread of the viral DNA. A proline-rich extensin-like receptor protein kinase (PERK) was found to interact specifically with NSP of Cabbage leaf curl virus (CaLCuV) and of tomato-infecting geminiviruses through a yeast two-hybrid screening. The PERK-like protein, which we designated NsAK (for NSP-associated kinase), is structurally organized into a proline-rich N-terminal domain, followed by a transmembrane segment and a C-terminal serine/threonine kinase domain. The viral protein interacted stably with defective versions of the NsAK kinase domain, but not with the potentially active enzyme, in an in vitro binding assay. In vitro-translated NsAK enhanced the phosphorylation level of NSP, indicating that NSP functions as a substrate for NsAK. These results demonstrate that NsAK is an authentic serine/threonine kinase and suggest a functional link for NSP-NsAK complex formation. This interpretation was corroborated by in vivo infectivity assays showing that loss of NsAK function reduces the efficiency of CaLCuV infection and attenuates symptom development. Our data implicate NsAK as a positive contributor to geminivirus infection and suggest it may regulate NSP function.

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STK39 is differentially expressed in the brains of patients with schizophrenia.

10.31219/osf.io/hakr7 ◽

2020 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Frontal Cortex ◽

Schizoaffective Disorder ◽

Psychotic Disorders ◽

Auditory Hallucinations ◽

Differentially Expressed ◽

Serine Threonine Kinase ◽

Significant Differential Expression ◽

Threonine Kinase ◽

Microarray Datasets ◽

Cardinal Feature

Visual and auditory hallucinations are a cardinal feature of psychotic disorders (1). We mined published and public microarray datasets (2, 3) to discover differentially expressed genes in schizophrenia and schizoaffective disorder. We found significant differential expression of the serine/threonine kinase 39, STK39, in neurons of the dorsolateral pre-frontal cortex from patients with schizophrenia and schizoaffective disorder.

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Receptor protein serine/threonine kinase

Springer Handbook of Enzymes ◽

10.1007/978-3-540-85701-3_14 ◽

2009 ◽

pp. 340-354

Keyword(s):

Receptor Protein ◽

Serine Threonine Kinase ◽

Threonine Kinase

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Differential expression of BUB1 mitotic checkpoint serine/threonine kinase in cancers of the breast.

10.31219/osf.io/juz37 ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Differential Expression ◽

Survival Data ◽

Mitotic Checkpoint ◽

Normal Breast ◽

Differentially Expressed ◽

Serine Threonine Kinase ◽

Significant Differential Expression ◽

Primary Tumors ◽

Threonine Kinase

Breast cancer affects women at relatively high frequency (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding BUB1 mitotic checkpoint serine/threonine kinase, BUB1, when comparing primary tumors of the breast to the tissue of origin, the normal breast. BUB1 was also differentially expressed in the tumor cells of patients with triple negative breast cancer. BUB1 mRNA was present at significantly higher quantities in tumors of the breast as compared to normal breast tissue. Analysis of human survival data revealed that expression of BUB1 in primary tumors of the breast was correlated with distant metastasis-free survival in patients with luminal A subtype cancer. BUB1 may be of relevance to initiation, maintenance or progression of cancers of the female breast.

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STRADα Regulates LKB1 Localization by Blocking Access to Importin-α, and by Association with Crm1 and Exportin-7

Molecular Biology of the Cell ◽

10.1091/mbc.e07-05-0454 ◽

2008 ◽

Vol 19 (4) ◽

pp. 1614-1626 ◽

Cited By ~ 69

Author(s):

Julia Dorfman ◽

Ian G. Macara

Keyword(s):

Catalytic Activity ◽

Cell Polarity ◽

Nuclear Export ◽

Nucleocytoplasmic Transport ◽

Cellular Distribution ◽

Nucleocytoplasmic Shuttling ◽

Serine Threonine Kinase ◽

Threonine Kinase ◽

Importin Α ◽

Export Receptors

LKB1, a serine/threonine kinase, regulates cell polarity, metabolism, and cell growth. The activity and cellular distribution of LKB1 are determined by cofactors, STRADα and MO25. STRADα induces relocalization of LKB1 from the nucleus to the cytoplasm and stimulates its catalytic activity. MO25 stabilizes the STRADα/LKB1 interaction. We investigated the mechanism of nucleocytoplasmic transport of LKB1 in response to its cofactors. Although LKB1 is imported into the nucleus by importin-α/β, STRADα and MO25 passively diffuse between the nucleus and the cytoplasm. STRADα induces nucleocytoplasmic shuttling of LKB1. STRADα facilitates nuclear export of LKB1 by serving as an adaptor between LKB1 and exportins CRM1 and exportin7. STRADα inhibits import of LKB1 by competing with importin-α for binding to LKB1. MO25 stabilizes the LKB1–STRADα complex but it does not facilitate its nucleocytoplasmic shuttling. Strikingly, the STRADβ, isoform which differs from STRADα in the N- and C-terminal domains that are responsible for interaction with export receptors, does not efficiently relocalize LKB1 from the nucleus to the cytoplasm. These results identify a multifactored mechanism to control LKB1 localization, and they suggest that the STRADβ-LKB1 complex might possess unique functions in the nucleus.

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