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Related Experiment Video

Updated: Jul 5, 2026

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes

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Published on: September 28, 2018

SHPS-1/SIRP1alpha contributes to interleukin-6 signalling.

Radoslaw M Sobota¹, Pia J Müller, Christina Khouri

¹Department of Biochemistry, RWTH Aachen University, Pauwelsstrasse 30, D-52074 Aachen, Germany.

Cellular Signalling

|May 3, 2008

Summary

Signal regulatory protein alpha (SIRP1alpha) influences interleukin-6 (IL-6) signaling by regulating SHP2 phosphorylation. This balance impacts ERK and STAT3 activation, crucial for cell responses in diseases.

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Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors

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Published on: July 17, 2020

Area of Science:

Cellular signaling
Immunology
Molecular biology

Background:

Signal regulatory protein alpha (SIRP1alpha/SHPS-1) is a transmembrane glycoprotein involved in growth factor and cell adhesion signaling.
The role of SIRP1alpha in interleukin-6 (IL-6) type cytokine signaling remains largely unexplored.

Purpose of the Study:

To investigate the contribution of SIRP1alpha to IL-6 type cytokine signaling.
To elucidate the mechanism by which SIRP1alpha modulates IL-6 induced cellular responses.

Main Methods:

Utilized mouse embryonic fibroblasts (MEFs) with varying SIRP1alpha expression (wild-type and deficient).
Analyzed protein tyrosine phosphatase SHP2 phosphorylation, ERK1/2 activation, and STAT3 activation/phosphorylation.
Assessed STAT3-dependent gene induction in response to IL-6 stimulation.

Main Results:

SIRP1alpha binds SHP2 in an IL-6 stimulation-dependent manner.
SIRP1alpha deficiency enhances SHP2 phosphorylation but delays STAT3 activation and reduces STAT3-dependent gene induction.
SIRP1alpha counteracts SHP2 phosphorylation, influencing ERK activation and STAT3 transactivation.

Conclusions:

SIRP1alpha plays a critical role in modulating IL-6 signaling pathways.
The findings highlight SIRP1alpha's function in balancing MAPK and STAT3 activation in response to IL-6.
Dysregulation of this balance is implicated in autoimmune diseases, inflammatory conditions, and cancer.