Casitas B-lineage lymphoma mutants activate AKT to induce transformation in cooperation with class III receptor tyrosine kinases

2013 ◽  
Vol 41 (3) ◽  
pp. 271-280.e4 ◽  
Author(s):  
Harald Polzer ◽  
Hanna Janke ◽  
Diana Schmid ◽  
Wolfgang Hiddemann ◽  
Karsten Spiekermann
Keyword(s):  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Class Iii ◽  
B Lineage

scholarly journals Class III Receptor Tyrosine Kinases in Acute Leukemia – Biological Functions and Modern Laboratory Analysis

2015 ◽  
Vol 10s3 ◽  
pp. BMI.S22433 ◽  
Author(s):  
Rimma Berenstein
Keyword(s):  
Tyrosine Kinases ◽  
Complex Disease ◽  
Receptor Tyrosine Kinases ◽  
Physiological Role ◽  
Leukemic Cells ◽  
World Health ◽  
Laboratory Diagnostics ◽  
Screening Methods ◽  
Class Iii ◽  
Short Period

Acute myeloid leukemia (AML) is a complex disease caused by deregulation of multiple signaling pathways. Mutations in class III receptor tyrosine kinases (RTKs) have been implicated in alteration of cell signals concerning the growth and differentiation of leukemic cells. Point mutations, insertions, or deletions of RTKs as well as chromosomal translocations induce constitutive activation of the receptor, leading to uncontrolled proliferation of undifferentiated myeloid blasts. Aberrations can occur in all domains of RTKs causing either the ligand-independent activation or mimicking the activated conformation. The World Health Organization recommended including RTK mutations in the AML classification since their detection in routine laboratory diagnostics is a major factor for prognostic stratification of patients. Polymerase chain reaction (PCR)–based methods are well-validated for the detection of fms-related tyrosine kinase 3 ( FLT3) mutations and can easily be applied for other RTKs. However, when methodological limitations are reached, accessory techniques can be applied. For a higher resolution and more quantitative approach compared to agarose gel electrophoresis, PCR fragments can be separated by capillary electrophoresis. Furthermore, high-resolution melting and denaturing high-pressure liquid chromatography are reliable presequencing screening methods that reduce the sample amount for Sanger sequencing. Because traditional DNA sequencing is time-consuming, next-generation sequencing (NGS) is an innovative modern possibility to analyze a high amount of samples simultaneously in a short period of time. At present, standardized procedures for NGS are not established, but when this barrier is resolved, it will provide a new platform for rapid and reliable laboratory diagnostic of RTK mutations in patients with AML. In this article, the biological and physiological role of RTK mutations in AML as well as possible laboratory methods for their detection will be reviewed.

scholarly journals The Oncogenic Signaling Disruptor, NDRG1: Molecular and Cellular Mechanisms of Activity

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2382 ◽  
Author(s):  
Jason Chekmarev ◽  
Mahan Gholam Azad ◽  
Des R. Richardson
Keyword(s):  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Tumor Development ◽  
Pancreatic Tumors ◽  
Cellular Mechanisms ◽  
Oncogenic Signaling ◽  
Tumor Growth And Metastasis ◽  
B Lineage ◽  
Cbl Protein ◽  
Docking Protein

NDRG1 is an oncogenic signaling disruptor that plays a key role in multiple cancers, including aggressive pancreatic tumors. Recent studies have indicated a role for NDRG1 in the inhibition of multiple tyrosine kinases, including EGFR, c-Met, HER2 and HER3, etc. The mechanism of activity of NDRG1 remains unclear, but to impart some of its functions, NDRG1 binds directly to key effector molecules that play roles in tumor suppression, e.g., MIG6. More recent studies indicate that NDRG1s-inducing drugs, such as novel di-2-pyridylketone thiosemicarbazones, not only inhibit tumor growth and metastasis but also fibrous desmoplasia, which leads to chemotherapeutic resistance. The Casitas B-lineage lymphoma (c-Cbl) protein may be regulated by NDRG1, and is a crucial E3 ligase that regulates various protein tyrosine and receptor tyrosine kinases, primarily via ubiquitination. The c-Cbl protein can act as a tumor suppressor by promoting the degradation of receptor tyrosine kinases. In contrast, c-Cbl can also promote tumor development by acting as a docking protein to mediate the oncogenic c-Met/Crk/JNK and PI3K/AKT pathways. This review hypothesizes that NDRG1 could inhibit the oncogenic function of c-Cbl, which may be another mechanism of its tumor-suppressive effects.

scholarly journals Regulation of Beclin 1-Mediated Autophagy by Oncogenic Tyrosine Kinases

2020 ◽  
Vol 21 (23) ◽  
pp. 9210
Author(s):  
Silvia Vega-Rubín-de-Celis ◽  
Lisa Kinch ◽  
Samuel Peña-Llopis
Keyword(s):  
Tyrosine Phosphorylation ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Current Knowledge ◽  
Beclin 1 ◽  
Class Iii ◽  
Core Component ◽  
Post Translational Modifications ◽  
Autophagy Activity

Beclin 1 is a major regulator of autophagy, and it is a core component of the class III PI3K complexes. Beclin 1 is a highly conserved protein and its function is regulated in a number of ways, including post-translational modifications. Several studies indicate that receptor and non-receptor tyrosine kinases regulate autophagy activity in cancer, and some suggest the importance of Beclin 1 tyrosine phosphorylation in this process. Here we summarize the current knowledge of the mechanism whereby some oncogenic tyrosine kinases regulate autophagy through Beclin 1.

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