10,338 results match your criteria serine-threonine tyrosine

Involvement of Phosphatases in Parasite Biology and Pathogeny.

Front Cell Infect Microbiol 2021 22;11:633146. Epub 2021 Apr 22.

Instituto de Bioquímica Médica Leopoldo De Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

In the lifecycle, the motile promastigote form is transmitted from the sand fly vector to a mammalian host during a blood meal. Inside vertebrate host macrophages, the parasites can differentiate into the amastigote form and multiply, causing leishmaniasis, one of the most significant neglected tropical diseases. parasites face different conditions throughout their development inside sand flies. Read More

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Adequacy of small biopsy and cytology specimens for comprehensive genomic profiling of patients with non-small-cell lung cancer to determine eligibility for immune checkpoint inhibitor and targeted therapy.

J Clin Pathol 2021 May 5. Epub 2021 May 5.

Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

Aims: In advanced-stage non-small-cell lung cancer (NSCLC), incomplete genotyping for guideline-recommended genomic biomarkers poses a significant challenge to making informed and timely clinical decisions. We report our institution's experience in assessing the adequacy of small specimens for comprehensive genomic profiling for guideline-recommended lung cancer biomarker testing.

Methods: We performed a retrospective evaluation of all image-guided procedures for NSCLC performed in our institution between October 2016 and July 2018, including core needle biopsy (CNB) and fine-needle aspiration (FNA) in patients who had undergone genomic profiling for lung cancer. Read More

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Protein Serine/Threonine Phosphatase Type 2C of .

Front Cell Infect Microbiol 2021 15;11:641356. Epub 2021 Apr 15.

Unidad de Investigación UNAM-INC, División de Investigación, Facultad de Medicina, Instituto Nacional de Cardiología Ignacio Chávez., Ciudad de México, Mexico.

Protein phosphorylation and dephosphorylation are increasingly recognized as important processes for regulating multiple physiological mechanisms. Phosphorylation is carried out by protein kinases and dephosphorylation by protein phosphatases. Phosphoprotein phosphatases (PPPs), one of three families of protein serine/threonine phosphatases, have great structural diversity and are involved in regulating many cell functions. Read More

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Comparative Phosphoproteomics of Classical Bordetellae Elucidates the Potential Role of Serine, Threonine and Tyrosine Phosphorylation in Biology and Virulence.

Front Cell Infect Microbiol 2021 13;11:660280. Epub 2021 Apr 13.

School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia.

The genus is divided into two groups: classical and non-classical. , and are known as classical bordetellae, a group of important human pathogens causing whooping cough or whooping cough-like disease and hypothesized to have evolved from environmental non-classical bordetellae. infections have increased globally driving the need to better understand these pathogens for the development of new treatments and vaccines. Read More

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DYRK1A Negatively Regulates CDK5-SOX2 Pathway and Self-Renewal of Glioblastoma Stem Cells.

Int J Mol Sci 2021 Apr 13;22(8). Epub 2021 Apr 13.

Charles Perkins Centre and School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.

Glioblastoma display vast cellular heterogeneity, with glioblastoma stem cells (GSCs) at the apex. The critical role of GSCs in tumour growth and resistance to therapy highlights the need to delineate mechanisms that control stemness and differentiation potential of GSC. Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) regulates neural progenitor cell differentiation, but its role in cancer stem cell differentiation is largely unknown. Read More

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Targeting Protein Kinases in Blood Cancer: Focusing on CK1α and CK2.

Int J Mol Sci 2021 Apr 2;22(7). Epub 2021 Apr 2.

Department of Medicine, Hematology Section, University of Padova, Via N. Giustiniani 2, 35128 Padova, Italy.

Disturbance of protein kinase activity may result in dramatic consequences that often lead to cancer development and progression. In tumors of blood origin, both tyrosine kinases and serine/threonine kinases are altered by different types of mutations, critically regulating cancer hallmarks. CK1α and CK2 are highly conserved, ubiquitously expressed and constitutively active pleiotropic kinases, which participate in multiple biological processes. Read More

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Profiling Oncogenic Germline Mutations in Unselected Chinese Lung Cancer Patients.

Front Oncol 2021 7;11:647598. Epub 2021 Apr 7.

Department of Thoracic Surgery, Affiliated Hospital of Hebei University, Baoding, China.

Introduction: Emerging evidence has suggested that inherited factors are also involved in lung cancer development. However, most studies focused on well-elucidated cancer predisposition genes, the majority of which are tumor suppressor genes. The profile of germline mutations in oncogenic driver genes remains unrevealed, which might also provide potential clinical implications for lung cancer management. Read More

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Disruption of the HER3-PI3K-mTOR oncogenic signaling axis and PD-1 blockade as a multimodal precision immunotherapy in head and neck cancer.

Nat Commun 2021 04 22;12(1):2383. Epub 2021 Apr 22.

Moores Cancer Center, University of California San Diego, La Jolla, CA, USA.

Immune checkpoint blockade (ICB) therapy has revolutionized head and neck squamous cell carcinoma (HNSCC) treatment, but <20% of patients achieve durable responses. Persistent activation of the PI3K/AKT/mTOR signaling circuitry represents a key oncogenic driver in HNSCC; however, the potential immunosuppressive effects of PI3K/AKT/mTOR inhibitors may limit the benefit of their combination with ICB. Here we employ an unbiased kinome-wide siRNA screen to reveal that HER3, is essential for the proliferation of most HNSCC cells that do not harbor PIK3CA mutations. Read More

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Actionable driver DNA variants and fusion genes can be detected in archived cytological specimens with the Oncomine Dx Target Test Multi-CDx system in lung cancer.

Cancer Cytopathol 2021 Apr 19. Epub 2021 Apr 19.

Department of Gastroenterology, Yamanashi Central Hospital, Kofu, Japan.

Background: Molecular testing is critical for identifying actionable variants in lung cancer for precision medicine. When tumor tissue samples are unavailable, archived cytological specimens (ACSs) can be used. The authors examined whether oncogenic variants could be accurately detected in ACSs versus paired formalin-fixed, paraffin-embedded (FFPE) tumor tissues with in vitro diagnostic tests. Read More

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Overexpression of rice OsWNK9 promotes arsenite tolerance in transgenic Arabidopsis plants.

J Biotechnol 2021 May 14;332:114-125. Epub 2021 Apr 14.

Nuclear Agriculture and Biotechnology Division, Bhabha Atomic Research Centre, Mumbai, 400084, India. Electronic address:

Protein kinases are involved in the transfer of phosphate group to serine, threonine, and tyrosine residues of a target protein. With No Lysine (WNK) kinase is a member of the serine/threonine protein kinase family, which has conserved catalytic lysine (K) residue in subdomain I instead of being in subdomain II.The WNKs family members in plants are stress inducible and have been validated for their role in abiotic stress tolerance. Read More

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Mechanism of Electroacupuncture Regulating IRS-1 Phosphorylation in Skeletal Muscle to Improve Insulin Sensitivity.

Evid Based Complement Alternat Med 2021 22;2021:8631475. Epub 2021 Mar 22.

Beijing University of Chinese Medicine, Beijing 100029, China.

Objective: To explore the possible mechanism of electroacupuncture to improve insulin sensitivity in type 2 diabetes rats.

Methods: Fourteen Zucker Diabetic Fatty (ZDF) rats were randomly divided into two groups: a model group and an electroacupuncture group, with 7 rats in each group. Seven Zucker Lean (ZL) rats served as a control group. Read More

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Dual Specificity Kinase DYRK3 Promotes Aggressiveness of Glioblastoma by Altering Mitochondrial Morphology and Function.

Int J Mol Sci 2021 Mar 15;22(6). Epub 2021 Mar 15.

Department of Integrated Biological Science, Pusan National University, Busan 46241, Korea.

Glioblastoma multiforme (GBM) is a malignant primary brain tumor with poor patient prognosis. Although the standard treatment of GBM is surgery followed by chemotherapy and radiotherapy, often a small portion of surviving tumor cells acquire therapeutic resistance and become more aggressive. Recently, altered kinase expression and activity have been shown to determine metabolic flux in tumor cells and metabolic reprogramming has emerged as a tumor progression regulatory mechanism. Read More

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LATS1 Is a Mediator of Melanogenesis in Response to Oxidative Stress and Regulator of Melanoma Growth.

Int J Mol Sci 2021 Mar 18;22(6). Epub 2021 Mar 18.

Department of Cancer Immunology, Chair of Medical Biotechnology, Poznan University of Medical Sciences, Rokietnicka Street 8, 61-806 Poznan, Poland.

The LATS1 kinase has been described as a tumor suppressor in various cancers. However, its role in melanoma has not been fully elucidated. There are several processes involved in tumorigenesis, including melanin production. Read More

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Modulation of Gene Expression in Actinobacteria by Translational Modification of Transcriptional Factors and Secondary Metabolite Biosynthetic Enzymes.

Front Microbiol 2021 16;12:630694. Epub 2021 Mar 16.

Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, Mexico.

Different types of post-translational modifications are present in bacteria that play essential roles in bacterial metabolism modulation. Nevertheless, limited information is available on these types of modifications in actinobacteria, particularly on their effects on secondary metabolite biosynthesis. Recently, phosphorylation, acetylation, or phosphopantetheneylation of transcriptional factors and key enzymes involved in secondary metabolite biosynthesis have been reported. Read More

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Properties of FDA-approved small molecule phosphatidylinositol 3-kinase inhibitors prescribed for the treatment of malignancies.

Robert Roskoski

Pharmacol Res 2021 Mar 26;168:105579. Epub 2021 Mar 26.

Blue Ridge Institute for Medical Research, 3754 Brevard Road, Suite 116, Box 19, Horse Shoe, NC 28742-8814, United States. Electronic address:

The discovery of the phosphatidylinositol 3-kinase (PI 3-kinase) pathway was a major advance in understanding eukaryotic signal transduction. The high frequency of PI 3-kinase pathway mutations in many cancers stimulated the development of drugs targeting these oncogenic mutants. The PI 3-kinases are divided into three classes and Class I PI 3-kinases, which catalyze the phosphorylation of phosphatidylinositol-4,5-bisphosphate (PI-4,5-P2) to generate phosphatidylinositol-3,4,5-trisphosphate (PIP3), are the main subject of this review. Read More

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Evaluation of the neurotoxic effects of engineered nanomaterials in C57BL/6J mice in 28-day oral exposure studies.

Neurotoxicology 2021 May 23;84:155-171. Epub 2021 Mar 23.

IUF - Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany. Electronic address:

In recent years, concerns have emerged about the potential neurotoxic effects of engineered nanomaterials (NMs). Titanium dioxide and silver are among the most widely used types of metallic NMs. We have investigated the effects of these NMs on behaviour and neuropathology in male and female C57BL/6J mice following 28-day oral exposure with or without a 14-day post-exposure recovery. Read More

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NGF nanoparticles enhance the potency of transplanted human umbilical cord mesenchymal stem cells for myocardial repair.

Am J Physiol Heart Circ Physiol 2021 May 26;320(5):H1959-H1974. Epub 2021 Mar 26.

Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

In this study, we investigated whether human umbilical cord mesenchymal stem cell (hUCMSC) fibrin patches loaded with nerve growth factor (NGF) poly(lactic--glycolic acid) (PLGA) nanoparticles could enhance the therapeutic potency of hUCMSCs for myocardial infarction (MI). In vitro, NGF significantly improved the proliferation of hUCMSCs and mitigated cytotoxicity and apoptosis under hypoxic injury. NGF also promoted the paracrine effects of hUCMSCs on angiogenesis and cardiomyocyte protection. Read More

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NleB/SseKs ortholog effectors as a general bacterial monoglycosyltransferase for eukaryotic proteins.

Curr Opin Struct Biol 2021 Mar 21;68:215-223. Epub 2021 Mar 21.

Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea. Electronic address:

Protein glycosylation is the most common post-translational modification as more than 50% of all human proteins are glycosylated. Pathogenic bacteria glycosylation allows adhesion to host cells and manipulates eukaryotic functions. A variety of acceptor proteins in bacterial glycosylation was recently discovered. Read More

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Recent advances in development of hetero-bivalent kinase inhibitors.

Eur J Med Chem 2021 Apr 23;216:113318. Epub 2021 Feb 23.

College of Pharmacy, Pusan National University, Busan, 46241, Republic of Korea. Electronic address:

Identifying a pharmacological agent that targets only one of more than 500 kinases present in humans is an important challenge. One potential solution to this problem is the development of bivalent kinase inhibitors, which consist of two connected fragments, each bind to a dissimilar binding site of the bisubstrate enzyme. The main advantage of bivalent (type V) kinase inhibitors is generating more interactions with target enzymes that can enhance the molecules' selectivity and affinity compared to single-site inhibitors. Read More

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ACK1 is dispensable for development, skin tumor formation, and breast cancer cell proliferation.

FEBS Open Bio 2021 Mar 17. Epub 2021 Mar 17.

Biotech Research and Innovation Center (BRIC), University of Copenhagen, Denmark.

Activated Cdc42-associated kinase 1 (ACK1), a widely expressed nonreceptor tyrosine kinase, is often amplified in cancer and has been shown to interact with Cell division cycle 42 (Cdc42), Epidermal growth factor receptor (EGFR), and several other cancer-relevant molecules, suggesting a possible role for ACK1 in development and tumor formation. To directly address this scenario, we generated mice lacking a functional ACK1 gene (ACK1 ko) using CRISPR genome editing. ACK1 ko mice developed normally, displayed no obvious defect in tissue maintenance, and were fertile. Read More

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Pathogenicity and virulence of Japanese encephalitis virus: Neuroinflammation and neuronal cell damage.

Virulence 2021 12;12(1):968-980

Department of Preventive Veterinary Medicine, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, Jiangxi, P. R. China.

Thousands of human deaths occur annually due to Japanese encephalitis (JE), caused by Japanese encephalitis virus. During the virus infection of the central nervous system, reactive gliosis, uncontrolled inflammatory response, and neuronal cell death are considered as the characteristic features of JE. To date, no specific treatment has been approved to overcome JE, indicating a need for the development of novel therapies. Read More

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December 2021

LIMK1 nuclear translocation promotes hepatocellular carcinoma progression by increasing p-ERK nuclear shuttling and by activating c-Myc signalling upon EGF stimulation.

Oncogene 2021 Apr 8;40(14):2581-2595. Epub 2021 Mar 8.

Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

LIM kinase 1 (LIMK1) is a serine/threonine and tyrosine kinase that is predominantly located in the cytoplasm. In our study, nuclear translocation of LIMK1 in clinical hepatocellular carcinoma (HCC) samples was demonstrated for the first time, especially in samples from those with intravascular tumour thrombus. LIMK1 was overexpressed in HCC tissues, and nuclear LIMK1 expression was associated with poor prognosis in HCC patients. Read More

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Regorafenib-Attenuated, Bleomycin-Induced Pulmonary Fibrosis by Inhibiting the TGF-β1 Signaling Pathway.

Int J Mol Sci 2021 Feb 17;22(4). Epub 2021 Feb 17.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, China.

Idiopathic pulmonary fibrosis (IPF) is a fatal and age-related pulmonary disease. Nintedanib is a receptor tyrosine kinase inhibitor, and one of the only two listed drugs against IPF. Regorafenib is a novel, orally active, multi-kinase inhibitor that has similar targets to nintedanib and is applied to treat colorectal cancer and gastrointestinal stromal tumors in patients. Read More

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February 2021

The Attenuated Secretion of Hyaluronan by UVA-Exposed Human Fibroblasts Is Associated with Up- and Downregulation of HYBID and HAS2 Expression via Activated and Inactivated Signaling of the p38/ATF2 and JAK2/STAT3 Cascades.

Int J Mol Sci 2021 Feb 19;22(4). Epub 2021 Feb 19.

Center for Bioscience Research & Education, Utsunomiya University, Tochigi 321-8505, Japan.

Little is known about the effects on hyaluronan (HA) metabolism of UVA radiation. This study demonstrates that the secretion of HA by human dermal fibroblasts (HDFs) is downregulated by UVA, accompanied by the down- and upregulation of mRNA and protein levels of the HA-synthesizing enzyme (HAS2) and the HA-degrading protein, HYaluronan Binding protein Involved in HA Depolymerization(HYBID), respectively. Signaling analysis revealed that the exposure distinctly elicits activation of the p38/MSK1/CREB/c-Fos/AP-1 axis, the JNK/c-Jun axis, and the p38/ATF-2 axis, but downregulates the phosphorylation of NF-kB and JAK/STAT3. Read More

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February 2021

5-Methoxybenzothiophene-2-Carboxamides as Inhibitors of Clk1/4: Optimization of Selectivity and Cellular Potency.

Molecules 2021 Feb 13;26(4). Epub 2021 Feb 13.

Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C2.3, D-66123 Saarbrücken, Germany.

Clks have been shown by recent studies to be promising targets for cancer therapy, as they are considered key regulators in the process of pre-mRNA splicing, which in turn affects every aspect of tumor biology. In particular, Clk1 and -4 are overexpressed in several human tumors. Most of the potent Clk1 inhibitors reported in the literature are non-selective, mainly showing off-target activity towards Clk2, Dyrk1A and Dyrk1B. Read More

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February 2021

Phosphorylation regulates cullin-based ubiquitination in tumorigenesis.

Acta Pharm Sin B 2021 Feb 19;11(2):309-321. Epub 2020 Sep 19.

Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.

Cullin-RING ligases (CRLs) recognize and interact with substrates for ubiquitination and degradation, and can be targeted for disease treatment when the abnormal expression of substrates involves pathologic processes. Phosphorylation, either of substrates or receptors of CRLs, can alter their interaction. Phosphorylation-dependent ubiquitination and proteasome degradation influence various cellular processes and can contribute to the occurrence of various diseases, most often tumorigenesis. Read More

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February 2021

[Screening of different metabolites in teenage football players after exercise fatigue].

Zhongguo Ying Yong Sheng Li Xue Za Zhi 2020 Sep;36(5):465-470

School of Sports, Shaanxi Normal University, Xi'an 710062, China.

To investigate the changes of metabolites of teenage football players after exercise-induced fatigue. Twelve male teenage football players (14~16 yrs) were selected as experimental subjects in this study. And an exercise model including aerobic and anaerobic exercise as one group exercise was established by using power bicycle: completion 6 min 150 W load, 60~65 r/min of riding exercise and 30 s of riding exercise which load was the maximum speed set by the tester's weight. Read More

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September 2020

Drug Screening of Potential Multiple Target Inhibitors for Estrogen Receptor-α-positive Breast Cancer.

In Vivo 2021 Mar-Apr;35(2):761-777

Chinese Medicine Research and Development Center, Center for Molecular Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan, R.O.C.;

Background/aim: Estrogen receptor α (ERα) antagonist is the most common treatment for ERα-positive breast cancer. However, compensatory signaling contributes to resistance to ERα antagonists. Thus, to explore the potential agents for targeting compensatory signaling, we screened multiple target inhibitors for breast cancer treatment. Read More

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October 2020

Dysregulation of Wnt/β-catenin signaling by protein kinases in hepatocellular carcinoma and its therapeutic application.

Cancer Sci 2021 May 6;112(5):1695-1706. Epub 2021 Apr 6.

Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Department of Hepatology, Institute of Hepatology and Metabolic Diseases, Institute of Integrated Chinese and Western Medicine for Oncology, The Affiliated Hospital of Hangzhou Normal University, College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, China.

Wnt/β-catenin signaling is indispensable for many biological processes, including embryonic development, cell cycle, inflammation, and carcinogenesis. Aberrant activation of the Wnt/β-catenin signaling can promote tumorigenicity and enhance metastatic potential in hepatocellular carcinoma (HCC). Targeting this pathway is a new opportunity for precise medicine for HCC. Read More

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HIV-1 Nef-Induced Secretion of the Proinflammatory Protease TACE into Extracellular Vesicles Is Mediated by Raf-1 and Can Be Suppressed by Clinical Protein Kinase Inhibitors.

J Virol 2021 04 12;95(9). Epub 2021 Apr 12.

Department of Virology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

Chronic immune activation is an important driver of human immunodeficiency virus type 1 (HIV-1) pathogenesis and has been associated with the presence of tumor necrosis factor-α converting enzyme (TACE) in extracellular vesicles (EVs) circulating in infected individuals. We have recently shown that activation of the Src-family tyrosine kinase hematopoietic cell kinase (Hck) by HIV-1 Nef can trigger the packaging of TACE into EVs via an unconventional protein secretion pathway. Using a panel of HIV-1 Nef mutants and natural HIV-2 and simian immunodeficiency virus (SIV) Nef alleles, we now show that the capacity to promote TACE secretion depends on the superior ability of HIV-1-like Nef alleles to induce Hck kinase activity, whereas other Nef effector functions are dispensable. Read More

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