Erythropoietin and IL-3 induce tyrosine phosphorylation of CrkL and its association with Shc, SHP-2, and Cbl in hematopoietic cells

Hiroshi Chin, Takako Saito, Ayako Arai, Koh Yamamoto, Ryuichi Kamiyama, Nobuyuki Miyasaka, Osamu Miura

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

The present study demonstrates that erythropoietin (Epo) and IL-3 induce tyrosine phosphorylation of the SH2/SH3-containing adapter protein CrkL and its transient association with tyrosine-phosphorylated SHP-2, Shc, and Cbl in a murine IL-3-dependent cell line, 32D, expressing the Epo receptor (EpoR). In these cells, CrkL was constitutively complexed with the guanine nucleotide exchange factor C3G, which was found to coimmunoprecipitate with Shc from Epo- or IL-3-stimulated cells. Studies using cells expressing mutant EpoRs showed that the Epo-induced tyrosine phosphorylation of CrkL is dependent on the membrane-proximal EpoR cytoplasmic region involved in the activation of Jak2 as well as the C-terminal 145 amino acid region which is required for tyrosine phosphorylation of SHP-2 and Shc. It was further revealed that CrkL is recruited to the tyrosine-phosphorylated EpoR, most likely through its interaction with tyrosine-phosphorylated Shc and SHP-2. These results suggest that CrkL is involved in the signaling pathways from the receptors for Epo and IL-3, most likely by modulating the activity of the Ras family GTPases through its interaction with C3G.

Original languageEnglish
Pages (from-to)412-417
Number of pages6
JournalBiochemical and biophysical research communications
Volume239
Issue number2
DOIs
Publication statusPublished - 1997 Oct 20
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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