Identification of a protein, SPY75, with repetitive helix-turn-helix motifs and an SH3 domain as a major substrate for protein tyrosine kinase(s) activated by FcεRI cross-linking

Hiromi Fukamachi, Nobuo Yamada, Toru Miura, Takashi Kato, Masaharu Ishikawa, Erich Gulbins, Amnon Altman, Yuko Kawakami, Toshiaki Kawakami

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Cross-linking of the high affinity receptor for IgE (FcεRI) initiates various biochemical and morphologic changes leading to degranulation and synthesis and release of cytokines and lipid mediators. Tyrosine phosphorylation of several cellular proteins was previously reported as the earliest signaling event for the FcεRI signal transduction pathway. By amino acid sequence determination and cDNA cloning analysis, a 75-kDa protein, termed SPY75, was identified as a major tyrosine-phosphorylated protein in activated mouse mast cells. SPY75, barely tyrosine phosphorylated in resting cells, was rapidly and transiently tyrosine phosphorylated on FcεRI cross- linking in an Ag concentration-dependent manner. Similar SPY75 tyrosine phosphorylation was observed when Ag receptors on B and T lymphocytes were cross-linked by appropriate antibodies. However, IL-3, granulocyte macrophage-CSF, or stem cell factor did not induce tyrosine phosphorylation of SPY75 in PT-18 mast cells, despite their responsiveness to these cytokines. SPY75 was not physically associated with the receptor or other known signaling molecules. This protein, the mouse homologue of the human HS1 gene product, has putative repetitive helix-turn-helix motifs found in many DNA-binding proteins and a putative nuclear transport signal. It also has a Src homology 3 domain, which is found in many signaling molecules and cytoskeletal proteins. These structural features and the rapid tyrosine phosphorylation on FcεRI cross-linking suggest that the signal generated by FcεRI cross-linking is transmitted through tyrosine phosphorylation of SPY75.

Original languageEnglish
Pages (from-to)642-652
Number of pages11
JournalJournal of Immunology
Volume152
Issue number2
Publication statusPublished - 1994 Jan 15
Externally publishedYes

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Helix-Turn-Helix Motifs
src Homology Domains
Protein-Tyrosine Kinases
Tyrosine
Phosphorylation
Proteins
Mast Cells
Cytokines
IgE Receptors
Stem Cell Factor
Cytoskeletal Proteins
Cell Nucleus Active Transport
Interleukin-3
Protein Sequence Analysis
DNA-Binding Proteins
Interleukin-1
Granulocytes
Organism Cloning
Signal Transduction
B-Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Identification of a protein, SPY75, with repetitive helix-turn-helix motifs and an SH3 domain as a major substrate for protein tyrosine kinase(s) activated by FcεRI cross-linking. / Fukamachi, Hiromi; Yamada, Nobuo; Miura, Toru; Kato, Takashi; Ishikawa, Masaharu; Gulbins, Erich; Altman, Amnon; Kawakami, Yuko; Kawakami, Toshiaki.

In: Journal of Immunology, Vol. 152, No. 2, 15.01.1994, p. 642-652.

Research output: Contribution to journalArticle

Fukamachi, Hiromi ; Yamada, Nobuo ; Miura, Toru ; Kato, Takashi ; Ishikawa, Masaharu ; Gulbins, Erich ; Altman, Amnon ; Kawakami, Yuko ; Kawakami, Toshiaki. / Identification of a protein, SPY75, with repetitive helix-turn-helix motifs and an SH3 domain as a major substrate for protein tyrosine kinase(s) activated by FcεRI cross-linking. In: Journal of Immunology. 1994 ; Vol. 152, No. 2. pp. 642-652.
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