Type II phosphatidylinositol 4-kinases interact with FcεRIγ subunit in RBL-2H3 cells.
Ligation of high-affinity IgE receptor I (FcεRI) on RBL-2H3 cells leads to recruitment of FcεRI and type II phosphatidylinositol 4-kinases (PtdIns 4-kinases) into lipid rafts. Lipid raft integrity is required for the activation of type II PtdIns 4-kinases and signal transduction through FcεRIγ during RBL-2H3 cell activation. However, the molecular mechanism by which PtdIns 4-kinases are coupled to FcεRI signaling is elusive. Here, we report association of type II PtdIns 4-kinase activity with FcεRIγ subunit in anti-FcεRIγ immunoprecipitates. FcεRIγ-associated PtdIns 4-kinase activity increases threefold upon FcεRI ligation in anti-FcεRIγ immunoprecipitates. Biochemical characterization of PtdIns 4-kinase activity associated with FcεRIγ reveals that it is a type II PtdIns 4-kinases. Canonical tyrosine residues mutation in FcεRIγ ITAM (Y65 and Y76) reveals that these two tyrosine residues in γ subunit are required for its interaction with type II PtdIns 4-kinases.
Department of Biosciences and Bioengineering, Wadhwani Research Centre, Indian Institute of Technology, Bombay, Powai, Mumbai, 400076, India, naveenb@u.washington.edu.
Naveen
N
Bojjireddy
Ranjeet Kumar
RK
Sinha
Gosukonda
G
Subrahmanyam
D000595:Amino Acid Sequence; D006801:Humans; D008407:Mast Cells / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism; D015778:Minor Histocompatibility Antigens; D009154:Mutation; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D017455:Receptors, IgE / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
D015778:Minor Histocompatibility Antigens; D017455:Receptors, IgE; D014443:Tyrosine; D017853:Phosphotransferases (Alcohol Group Acceptor); C402182:phosphatidylinositol phosphate 4-kinase