Fgr

Fgr is a Src family tyrosine kinase activated during β2 integrin-dependent signaling in human neutrophils, linking adhesion to protein tyrosine phosphorylation^[1]. Mechanistically, Fgr and Hck support adhesion-dependent neutrophil respiratory burst, spreading, and degranulation, showing that Fgr participates in integrin-driven inflammatory effector functions^[2]^[3]. Fgr also acts with Hck to negatively regulate neutrophil and dendritic-cell chemokine signaling through PIR-B, indicating a context-dependent role in myeloid signal control^[4]. In disease models, hematopoietic loss of Hck, Fgr, and Lyn protected mice from autoantibody-induced arthritis, blistering skin inflammation, and reverse passive Arthus reaction by impairing inflammatory-environment generation rather than intrinsic leukocyte recruitment^[5]. Compared with related Src family isoforms, Fgr shows substantial functional overlap with Hck and Lyn, because single Fgr deficiency did not block arthritis development, whereas combined Hck/Fgr/Lyn loss produced complete protection^[5]. For experimental applications, an Fgr kinase inhibitor attenuated sepsis-associated encephalopathy by reducing mitochondrial dysfunction, oxidative stress, and neuroinflammation through the SIRT1/PGC-1α pathway^[6].

References:

[1]. Berton G, et al. Beta 2 integrin-dependent protein tyrosine phosphorylation and activation of the FGR protein tyrosine kinase in human neutrophils. J Cell Biol. 1994 Aug;126(4):1111-21. [Content Brief]

[2]. Lowell CA, et al. Deficiency of Src family kinases p59/61hck and p58c-fgr results in defective adhesion-dependent neutrophil functions. J Cell Biol. 1996 May;133(4):895-910. [Content Brief]

[3]. Sibley CD, et al. Discovery of a Small Side Cavity in Sphingosine Kinase 2 that Enhances Inhibitor Potency and Selectivity. J Med Chem. 2020 Feb 13;63(3):1178-1198. [Content Brief]

[4]. Zhang H, et al. The Src family kinases Hck and Fgr negatively regulate neutrophil and dendritic cell chemokine signaling via PIR-B. Immunity. 2005 Feb;22(2):235-46. [Content Brief]

[5]. Kovács M, et al. The Src family kinases Hck, Fgr, and Lyn are critical for the generation of the in vivo inflammatory environment without a direct role in leukocyte recruitment. J Exp Med. 2014 Sep 22;211(10):1993-2011. [Content Brief]

[6]. Liu Y, et al. An Fgr kinase inhibitor attenuates sepsis-associated encephalopathy by ameliorating mitochondrial dysfunction, oxidative stress, and neuroinflammation via the SIRT1/PGC-1α signaling pathway. J Transl Med. 2023 Jul 20;21(1):486. [Content Brief]

Fgr Inhibitor (1)

Fgr Related Products (1):

Cat. No.	Product Name	Effect	Purity

HY-178014

SIK1-IN-1	Inhibitor
SIK1-IN-1 (Compound 27) is a selective Salt-inducible kinase 1 (SIK1) inhibitor with an IC₅₀ of 0.7  nM for SIK1 over SIK2 and SIK3. SIK1-IN-1 has no cytotoxicity against HEK293 cells and PBMCs (maximum concentration of 30 μM). SIK1-IN-1 also has potent inhibitory activities for 392 kinases, in particular tyrosine kinases, such as FGR, HCK and LYN).

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