Aggregation of the Fc epsilon RI in mast cells induces the synthesis of Fos-interacting protein and increases its DNA binding-activity: the dependence on protein kinase C-beta.
The ability of c-Fos to dimerize with various proteins creates transcription complexes which can exert their regulatory function on a variety of genes. One of the transcription factors that binds to c-Fos is the newly discovered Fos-interacting protein (FIP). In this report we present evidence for the regulation of the synthesis of FIP by a physiological stimulus. We found that the aggregation of the mast cell high affinity receptor for IgE (Fc epsilon RI) induced the synthesis of FIP and increased its DNA binding activity. Moreover, down-regulation of the isoenzyme protein kinase C-beta (PKC-beta) by a specific antisense phosphorothioate oligonucleotide resulted in profound inhibition of FIP-Fos DNA binding activity. Thus, aggregation of the Fc epsilon RI on mast cells elicits a PKC-beta dependent signaling pathway which regulates FIP-Fos DNA binding activity.
Lewin
I
I
Department of Biochemistry Hebrew University, Hadassah Medical School, Jerusalem, Israel.
Jacob-Hirsch
J
J
Zang
Z C
ZC
Kupershtein
V
V
Szallasi
Z
Z
Rivera
J
J
Razin
E
E
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000378:metabolism; D015723:Gene Library; D006801:Humans; D007073:Immunoglobulin E / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism*; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D017455:Receptors, IgE / Q000502:physiology*; D013873:Thionucleotides; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D051720:Upstream Stimulatory Factors
D017931:DNA Primers; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D016376:Oligonucleotides, Antisense; D017455:Receptors, IgE; D013873:Thionucleotides; D014157:Transcription Factors; C497184:USF2 protein, human; D051720:Upstream Stimulatory Factors; D007073:Immunoglobulin E; D011493:Protein Kinase C