Accelerate to discover

Back to filter

Related topics

Magnetic resonance elastography techniques and preclinical applications

Bruker Biospin

Sep 14, 2021

It has been known for centuries that tissue stiffness can change in the presence of disease, but quantifying such...

See What's Possible with the PippinHT

Sage Science

Sep 14, 2021

Programmable DNA size selection enables new discoveries by helping optimize the library detected by a sequencer. That’s...

Ex Vivo dental imaging is directly translatable to the clinic

Bruker Biospin

Sep 14, 2021

Although patients are too large in size for preclinical microCT scanners, it still has a big significance in clinical...

IncuCyte live cell analysis system for 3D Organoids discovery

Sartorius & Essen BioScience

Sep 10, 2021

Live-Cell Analysis has revolutionized numerous studies, with a wide selection of applications namely 3D Tumour Spheroid...

Sep 20, 2021

Blood-Brain Barrier (BBB) - Pathophysiology in ischemic stroke

RWD

Aug 27, 2021

In-depth Understanding of Blood-Brain Barrier (BBB)

Introducing New Aura 4.0 software

Spectral Instruments Imaging

Aug 27, 2021

With new features for both acquisition & analysis Aura Software enables you to capture and analyze your data quickly,...

Micro-CT user meeting 2021

Bruker Biospin

Aug 19, 2021

Year after year, the Micro-CT User meeting showcases state-of-the-art applications in both life and material sciences,...

Sep 20, 2021

Comparison of gamma and x-ray irradiation results

Precision X-Ray

Aug 12, 2021

Biological effects of Cs-137 and X-ray irradiators are comparable with regards to reconstitution chimerism in normal...

Show all topics (10)

Insulin receptor substrate 1 is a substrate of the Pim protein kinases

May 18, 2020

The Pim family of serine/threonine protein kinases (Pim 1, 2, and 3) contribute to cellular transformation by regulating glucose metabolism, protein synthesis, and mitochondrial oxidative phosphorylation. Drugs targeting the Pim protein kinases are being tested in phase I/II clinical trials for the treatment of hematopoietic malignancies. The goal of these studies was to identify Pim substrate(s) that could help define the pathway regulated by these enzymes and potentially serve as a biomarker of Pim activity. To identify novel substrates, bioinformatics analysis was carried out to identify proteins containing a consensus Pim phosphorylation site. This analysis identified the insulin receptor substrate 1 and 2 (IRS1/2) as potential Pim substrates.

Experiments were carried out in tissue culture, animals, and human samples from phase I trials to validate this observation and define the biologic readout of this phosphorylation. Our study demonstrates in both malignant and normal cells using either genetic or pharmacological inhibition of the Pim kinases or overexpression of this family of enzymes that human IRS1S1101 and IRS2S1149 are Pim substrates. In xenograft tumor experiments and in a human phase I clinical trial, a pan-Pim inhibitor administered in vivo to animals or humans decreased IRS1S1101 phosphorylation in tumor tissues. This phosphorylation was shown to have effects on the half-life of the IRS family of proteins, suggesting a role in insulin or IGF signaling. These results demonstrate that IRS1S1101 is a novel substrate for the Pim kinases and provide a novel marker for evaluation of Pim inhibitor therapy.

Do you want to learn more? Read the whole article!

Scientific paper
Application

Get more info

Miroslav Vecheta

Support specialist

Miroslav

Vecheta

+420 255 700 886

Send Message

Brand profile

Spectral Instruments Imaging

Spectral Instruments Imaging manufactures instruments for preclinical optical (bioluminescent, fluorescent) and X-ray imaging.

Related products

System for individual researchers and smaller specialist teams to conduct optical imaging studies in disease model progression, response to therapy, and cell migration in-vivo.

show detail

The Ami HT and Ami HTX (includes X-Ray imaging) optical imaging systems establish a new, high throughput benchmark for in vivo imaging suitable for specialist researchers and small teams.

show detail

The Lago and X‐Ray capable Lago X optical imaging systems provide a powerful and flexible in-vivo imaging capability suitable for imaging cores, specialist researchers and small teams, delivering an unmatched 10 mouse capacity across BLI, FLI and X‐Ray.

show detail

We supply and support Life-Science Technologies in the territory of Central and Eastern Europe.

Czech Republic

Slovakia

Hungary

Poland

Croatia

Slovenia

Serbia

Romania

Bulgaria

Latvia

Lithuania

Estonia

Russia

Ukraine

Belarus

Turkey