Cutting edge: association with I kappa B kinase beta regulates the subcellular localization of Homer3.
The signaling and adaptor protein Homer3 plays a role in controlling immune homeostasis and self-reactivity. Homer3 is recruited to the immune synapse (IS) following TCR ligation, although the mechanisms regulating this subcellular localization are unknown. We show that Homer3 specifically associates with a novel ubiquitin-like domain in the IkappaB kinase (IKK) beta subunit of the IKK complex. Homer3 associates with IKKbeta in T cells and colocalizes with the IKK complex at the IS. However, Homer3 is not required for IKK activation, as NF-kappaB signaling is intact in Homer3-deficient T cells. Instead, the IKK complex recruits Homer3 to the IS following TCR engagement, and we present evidence that this association regulates actin dynamics in T cells. These findings identify a novel interaction between two major signaling proteins and reveal an unexpected NF-kappaB-independent function for the IKK complex in regulating the subcellular localization of Homer3.
Yatherajam
Gayatri
G
Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Banerjee
Pinaki P
PP
McCorkell
Kelly A
KA
Solt
Laura A
LA
Hanson
Eric P
EP
Madge
Lisa A
LA
Kang
Shin
S
Worley
Paul F
PF
Orange
Jordan S
JS
May
Michael J
MJ
D002352:Carrier Proteins / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D006367:HeLa Cells; D000072233:Homer Scaffolding Proteins; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism* / Q000502:physiology; D054992:Immunological Synapses / Q000201:enzymology / Q000276:immunology; D019169:Jurkat Cells; D017434:Protein Structure, Tertiary; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology; D013347:Subcellular Fractions / Q000276:immunology / Q000378:metabolism; D025801:Ubiquitin / Q000737:chemistry / Q000378:metabolism
D002352:Carrier Proteins; C000606616:HOMER3 protein, human; D000072233:Homer Scaffolding Proteins; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D011948:Receptors, Antigen, T-Cell; D025801:Ubiquitin