Humans ; Phosphorylation ; Serine ; Protein Serine-Threonine Kinases/metabolism* ; Spasms, Infantile

Humans ; Phosphorylation ; Serine/metabolism* ; Protein Serine-Threonine Kinases/metabolism* ; Signal Transduction ; Neovascularization, Pathologic

Necroptosis is one of the regulated cell death, which involves receptor interacting protein kinase (RIPK) 1/RIPK3/mixed lineage kinase domain like protein (MLKL) signaling pathway. Among them, MLKL is the final execution of necroptosis. The formation of RIPK1/RIPK3/MLKL necrosome induces the phosphorylated MLKL, and the activated MLKL penetrates into the membrane bilayer to form membrane pores, which damages the integrity of the membrane and leads to cell death. In addition to participating in necroptosis, MLKL is also closely related to other cell death, such as NETosis, pyroptosis, and autophagy. Therefore, MLKL is involved in the pathological processes of various diseases related to abnormal cell death pathways (such as cardiovascular diseases, neurodegenerative diseases and cancer), and may be a therapeutic target of multiple diseases. Understanding the role of MLKL in different cell death can lay a foundation for seeking various MLKL-related disease targets, and also guide the development and application of MLKL inhibitors.
Protein Kinases/metabolism* ; Necroptosis/physiology* ; Receptor-Interacting Protein Serine-Threonine Kinases ; Signal Transduction ; Pyroptosis ; Apoptosis

In order to investigate the molecular mechanism of silk/threonine protein kinase (STK)-mediated blue light response in the algal Chlamydomonas reinhardtii, phenotype identification and transcriptome analysis were conducted for C. reinhardtii STK mutant strain crstk11 (with an AphvIII box reverse insertion in stk11 gene coding region) under blue light stress. Phenotypic examination showed that under normal light (white light), there was a slight difference in growth and pigment contents between the wild-type strain CC5325 and the mutant strain crstk11. Blue light inhibited the growth and chlorophyll synthesis in crstk11 cells, but significantly promoted the accumulation of carotenoids in crstk11. Transcriptome analysis showed that 860 differential expression genes (DEG) (559 up-regulated and 301 down-regulated) were detected in mutant (STK4) vs. wild type (WT4) upon treatment under high intensity blue light for 4 days. After being treated under high intensity blue light for 8 days, a total of 1 088 DEGs (468 upregulated and 620 downregulated) were obtained in STK8 vs. WT8. KEGG enrichment analysis revealed that compared to CC5325, the crstk11 blue light responsive genes were mainly involved in catalytic activity of intracellular photosynthesis, carbon metabolism, and pigment synthesis. Among them, upregulated genes included psaA, psaB, and psaC, psbA, psbB, psbC, psbD, psbH, and L, petA, petB, and petD, as well as genes encoding ATP synthase α, β and c subunits. Downregulated genes included petF and petJ. The present study uncovered that the protein kinase CrSTK11 of C. reinhardtii may participate in the blue light response of algal cells by mediating photosynthesis as well as pigment and carbon metabolism, providing new knowledge for in-depth analysis of the mechanism of light stress resistance in the algae.
Chlamydomonas reinhardtii/genetics* ; Photosynthesis/genetics* ; Plants/metabolism* ; Protein Kinases ; Threonine/metabolism* ; Carbon/metabolism* ; Serine/metabolism*

The innate immune system initiates innate immune responses by recognizing pathogen-related molecular patterns on the surface of pathogenic microorganisms through pattern recognition receptors. Through cascade signal transduction, it activates downstream transcription factors NF-κB and interferon regulatory factors (IRFs), and then leads to the production of inflammatory cytokines and type Ⅰ interferon, which resists the infection of pathogenic microorganism. TBK1 is a central adapter protein of innate immune signaling pathway and can activate both NF-κB and IRFs. It is a key protein kinase in the process of anti-infection. The finetuning regulation of TBK1 is essential to maintain immune homeostasis and resist pathogen invasion. This paper reviews the biological functions and ubiquitin modification of TBK1 in innate immunity, to provide theoretical basis for clinical treatment of pathogenic infections and autoimmune diseases.
Immunity, Innate ; Interferon Regulatory Factor-3/metabolism* ; Protein-Serine-Threonine Kinases/genetics* ; Signal Transduction ; Ubiquitin

The leucine-rich repeat kinase2 (LRRK2) has been identified to be the gene causing autosomal dominant inherited Parkinson's disease(PD)8. The clinical features of this type of PD are similar to those of idiopathic PD, but the pathological changes are diverse. The mutation types and frequencies of the LRRK2 distribute unevenly in different populations. LRRK2 is a large complex protein with multiple functions and expresses widely in human body. Sequence alignment shows that LRRK2 might be a multiple function kinase for substrate phosphorylation and might also act as a scaffolding protein. Further study on the physiological function and pathogenic mechanism of LRRK2 will help to find out the possible pathogenesis and new treatment for PD.
Animals ; Continental Population Groups ; genetics ; Humans ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 ; Mutation ; Parkinson Disease ; genetics ; pathology ; Protein-Serine-Threonine Kinases ; chemistry ; genetics ; metabolism ; Sequence Alignment

Adolescent ; Adult ; DNA ; genetics ; DNA Mutational Analysis ; Female ; Humans ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 ; Male ; Mutation ; Parkinsonian Disorders ; genetics ; metabolism ; Protein-Serine-Threonine Kinases ; genetics

This study aimed to investigate the effect and mechanisms of Ephedra Herb (EH) extract on adriamycin-induced nephrotic syndrome (NS), providing an experimental basis for the clinical treatment of NS. Hematoxylin and eosin staining, creatinine, urea nitrogen, and kidn injury molecule-1 were used to evaluate the activities of EH extract on renal function. The levels of inflammatory factors and oxidative stress were detected by kits. The levels of reactive oxygen species, immune cells, and apoptosis were measured by flow cytometry. A network pharmacological approach was used to predict the potential targets and mechanisms of EH extract in the treatment of NS. The protein levels of apoptosis-related proteins and CAMKK2, p-CAMKK2, AMPK, p-AMPK, mTOR and p-mTOR in the kidneys were detected by Western blot. The effective material basis of EH extract was screened by MTT assay. The AMPK pathway inhibitor (compound C, CC) was added to investigate the effect of the potent material basis on adriamycin-induced cell injury. EH extract significantly improved renal injury and relieve inflammation, oxidative stress, and apoptosis in rats. Network pharmacology and Western blot results showed that the effect of EH extract on NS may be associated with the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine significantly ameliorated adriamycin-induced NRK-52e cell injury. Methylephedrine also significantly improved the phosphorylation of AMPK and mTOR, which were blocked by CC. In sum, EH extract may ameliorate renal injury via the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine may be one of the material bases of EH extract.
Rats ; Animals ; Doxorubicin/adverse effects* ; Nephrotic Syndrome ; AMP-Activated Protein Kinases/metabolism* ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism* ; Apoptosis

OBJECTIVETo investigate the expression patterns of integrin-linked kinase (ILK) in oral squamous cell carcinoma (OSCC).

METHODSThe expression of ILK in 170 OSCC cases was examined by immunohistochemistry and periodic acid-schiff histochemistry.

RESULTSILK immunoreactivity occurred in cancer cells and(or) stroma encircling the malignant tissue. Along with the deteriorated histopathologic grade of oral cancer, there was stepwise aberration exhibiting from ILK-negative, to ILK-positive in epithelia, to ILK-positive in both epithelia and stroma, and to ILK-positive in stroma. Through non-parameter test, in both lymphatic invasion [ILK-positive in stroma in well-differentiated, moderately-differentiated and poorly-differentiated is 2% (1/50), 18% (6/33) and 64% (18/28), respectively] and non-lymphatic invasion group [ILK-positive in stroma in well-differentiated, moderately-differentiated and poorly-differentiated is 16% (4/25), 9/18 and 10/16, respectively), the expression patterns of ILK exhibited significant correlations with histopathology (F = 17.742, P < 0.001, F = 4.394, P = 0.017). ILK expression between lymphatic metastasis and non-lymphatic metastasis group was significantly different (χ(2) = 14.418, P = 0.002).

CONCLUSIONSILK inclines to express in stroma during the OSCC progress.

Carcinoma, Squamous Cell ; metabolism ; Cell Differentiation ; Epithelial Cells ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Mouth Neoplasms ; metabolism ; Protein-Serine-Threonine Kinases ; metabolism

OBJECTIVE: To investigate the expression of 2-type small conductance-Ca-activating-K (SK2) channel protein in hypertensive rat myocardial cells. METHODS: Twelve healthy adult male SD rats were randomly divided into control group (n=5) and experimental group (n=7). The rats of experimental group were injected intraperitoneally with N'-nitro-L-arginine (L-NNA 15 mg/(kg·d))while the rats of control group were injected intraperitoneally with isometrical normal saline(15 ml/(kg·d )). The body weight, blood pressure and electrocardiogram of the rats were measured every week. After 4 weeks, the rats were sacrificed to obtain hearts, and the expression of SK2 channel protein in myocardium was detected by Western blot. RESULTS: After 4 weeks of administration, compared with the control group, the blood pressure in the experimental group was significantly elevated (P＜0.05), QRS duration and R-R interval were prolonged, and the expressions of SK2 channel in the atrial and ventricular tissue of the experimental group were significantly higher than those in the control group (1.12±0.18,1.64±0.26, P ＜ 0.05). CONCLUSION The expressions of atrial and ventricular SK2 pathway are increased in hypertensive model rats. It may be one of the mechanism leading to arrhythmias in hypertensive model rats and can provide new ideas and strategies for the treatment and prognosis of hypertensive diseases.
Animals ; Hypertension ; metabolism ; Male ; Myocardium ; metabolism ; Protein-Serine-Threonine Kinases ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley