Homer-3 regulates activation of serum response element in T cells via its EVH1 domain.
Drosophila enabled/vasodilator-stimulated phosphoprotein (Ena/VASP) homology 1 (EVH1) domain proteins regulate signal transduction at the neuronal and immunologic synapse. Despite shared cell biologic machinery at these synapses, the regulation of client proteins that transmit synaptic activity to the nucleus is likely to be different. Homer-3, a member of the EVH1 family, is expressed in the thymus, suggesting a role for this protein in T-cell signal transduction. Upon T-cell receptor (TCR) engagement, Homer-3 was recruited to the contact area of Jurkat cells to anti-CD3 and CD28 antibody-coated beads prior to actin accumulation and was subsequently translocated into the nucleus. Overexpression of Homer-3 reduced transcriptional activation via the serum response element (SRE) in response to anti-CD3 antibody, phorbol ester, or dominant active Ha-Ras. Consistent with these results, knockdown of Homer-3 increased SRE activation. Homer-3 coprecipitated with CCAAT/enhancer binding protein beta (C/EBP beta), one of the transcription factors that binds to the SRE and has a consensus motif binding to EVH1 domain. Moreover, Homer-3 and its EVH1 domain fragment reduced transcriptional activation of C/EBP beta. These findings suggest that Homer-3 may be involved in the regulation of SRE activation in T cells via interaction between its EVH1 domain and C/EBP beta.
Ishiguro
Kazuhiro
K
Department of Medicine, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA.
Xavier
Ramnik
R
D000595:Amino Acid Sequence; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D016384:Consensus Sequence; D000072233:Homer Scaffolding Proteins; D006801:Humans; D019169:Jurkat Cells; D008156:Luciferases / Q000235:genetics; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D027602:Serum Response Element / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology*
D022762:CCAAT-Enhancer-Binding Proteins; D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D009479:Neuropeptides; D011948:Receptors, Antigen, T-Cell; C000606630:homer protein, Drosophila; D008156:Luciferases