Unique Phosphorylation Mechanism of Gab1 Using PI 3-Kinase as an Adaptor Protein

Grb2-associated binder-1 (Gab1) undergoes tyrosine phosphorylation in response to stimulation by growth factors and hormones including insulin, epidermal growth factor (EGF), nerve growth factor (NGF), and hepatocyte growth factor (HGF). However, the HGF receptor is the only one known to associate d...

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Published inBiochemical and biophysical research communications Vol. 288; no. 2; pp. 476 - 482
Main Authors Onishi-Haraikawa, Yukiko, Funaki, Makoto, Gotoh, Noriko, Shibuya, Masabumi, Inukai, Kouichi, Katagiri, Hideki, Fukushima, Yasushi, Anai, Motonobu, Ogihara, Takehide, Sakoda, Hideyuki, Ono, Hiraku, Kikuchi, Masatoshi, Oka, Yoshitomo, Asano, Tomoichiro
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 26.10.2001
Subjects
Adaptor Proteins, Signal Transducing
Animals
Cells, Cultured
CHO Cells
Cricetinae
EGF receptor
Gab1
Humans
Insecta
insulin receptor
Insulin Receptor Substrate Proteins
NGF receptor
phosphatidylinositol 3-kinase
Phosphatidylinositol 3-Kinases - metabolism
Phosphoproteins - chemistry
Phosphoproteins - metabolism
Phosphorylation
Protein Structure, Tertiary
Protein-Tyrosine Kinases - metabolism
receptor tyrosine kinase
NGF receptor
Gab1
EGF receptor
receptor tyrosine kinase
insulin receptor
phosphatidylinositol 3-kinase
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Summary:Grb2-associated binder-1 (Gab1) undergoes tyrosine phosphorylation in response to stimulation by growth factors and hormones including insulin, epidermal growth factor (EGF), nerve growth factor (NGF), and hepatocyte growth factor (HGF). However, the HGF receptor is the only one known to associate directly with Gab1. Herein, we explore the mechanism of Gab1 phosphorylation by other receptor protein-tyrosine kinases unable to bind to Gab1 directly. The Src homology 2 (SH2) domain of the phosphatidylinositol 3-kinase (PI3K) regulatory subunit binds Gab1 in a phosphorylation-independent manner. Moreover, the regulatory subunit of PI3K can mediate the association of Gab1 and receptor protein-tyrosine kinases including the insulin, EGF, and NGF receptors, all of which phosphorylate Gab1. Thus, it appears that the PI3K regulatory subunit acts as an adaptor protein via a phosphotyrosyl-independent SH2 interaction, allowing Gab1 to serve as a substrate for several tyrosine kinases. This is a new role for the PI3K regulatory subunit.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.2001.5791