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ARAP2 regulates the Interferon-gamma response by restricting SOCS1

ABSTRACT: Interferon-gamma (IFNγ) is a critical cytokine required to coordinate anti-viral immunity in response to pathogens such as influenza. IFNγ signals through the JAK-STAT pathway, inducing a tyrosine-phosphorylation cascade that ensures a potent immune response. Aberrant JAK-STAT signaling can drive hyperinflammation and autoimmunity, and thus signaling is tightly and selectively regulated by the IFNγ-inducible protein, Suppressor of Cytokine Signaling 1 (SOCS1). SOCS1 inhibits signaling by directly blocking JAK kinase activity. Here we identified a SOCS1-interacting partner, ARAP2 that fine-tunes SOCS1 function. We report that tyrosine 415 in ARAP2 binds the SOCS1-Src Homology 2 (SH2) domain and limits the ability of SOCS1 to inhibit IFNγ signaling. Our findings reveal ARAP2 as a key player in influenza immunity that promotes the IFNγ response through a phosphorylation dependent interaction with the negative regulator SOCS1.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Embryonic Stem Cell

SUBMITTER: Laura Dagley

LAB HEAD: Prof. Sandra Nicholson

PROVIDER: PXD060300 | Pride | 2025-10-06

REPOSITORIES: Pride

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			Action	DRS
	P3228_FL_1_1_1_1_01_5079.d.zip	Other
	P3228_FL_1_2_1_1_01_5080.d.zip	Other
	P3228_FL_1_3_1_1_01_5081.d.zip	Other
	P3228_GST_1_1_1_1_01_5071.d.zip	Other
	P3228_GST_1_2_1_1_01_5072.d.zip	Other

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