Open Accessc‐Cbl Is Inducibly Tyrosine‐phosphorylated by Epidermal Growth Factor Stimulation in Fibroblasts, and Constitutively Tyrosine‐phosphorylated and Associated with v‐Src in v‐ src ‐transformed Fibroblasts
Author(s) -
Odai Hideharu,
Sasaki Ko,
Hanazono Yutaka,
Ueno Hiroo,
Tanaka Tomoyuki,
Miyagawa Kiyoshi,
Mitani Kinuko,
Yazaki Yoshio,
Hirai Hisamaru
Publication year - 1995
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1995.tb03303.x
Subject(s) - proto oncogene tyrosine protein kinase src , tyrosine phosphorylation , biology , signal transduction , tyrosine kinase , phosphorylation , sh2 domain , epidermal growth factor , microbiology and biotechnology , grb2 , sh3 domain , tyrosine , receptor , biochemistry
The c‐cbl gene was cloned as the cellular homolog of the v ‐cbl oncogene that is the transforming component of a marine tumorigenic retrovirus, CAS NS‐1, though the biological roles of c‐Cbl remain to be elucidated. We have previously reported that c‐Cbl is implicated in the signal transduction triggered by granulocyte‐macrophage colony‐stimulating factor or erythropoietin in hematopoietic cells. Here, we observed tyrosine phosphorylation of c‐Cbl in cells expressing epidermal growth factor receptor depending on EGF stimulation and in v‐ src transformed cells. Furthermore, c‐Cbl was revealed to associate with v‐Src in vivo. By means of binding experiments using glutathione S‐transferase fusion proteins, we have found that the SH2 and SH3 domains of many proteins bind to c‐Cbl. These findings strongly suggest that c‐Cbl is implicated in a wide variety of signal transduction pathways, including those of EGF receptor and Src protein, as well as in the signaling pathways of hematopoietic cells.