Annexin II binds to SHP2 and this interaction is regulated by HSP70 levels.
The protein tyrosine phosphatase SHP2 is a positive effector of EGFR signaling. To improve our understanding of SHP2's function, we searched for additional binding proteins of SHP2. We found that Annexin II is an SHP2-binding protein. Physical interactions of SHP2 with Annexin II were confirmed in vivo. Furthermore, binding of SHP2 with Annexin II was regulated somewhat by EGF treatment and the extracellular Ca2+ chelator, EGTA. Previously, we reported that HSP70 levels can influence the binding of SHP2 with EGFR. Interestingly, increased HSP70 levels also inhibited the binding of SHP2 with Annexin II after EGF treatment in vivo. In addition, immunostaining experiments indicated that a fraction of SHP2 and Annexin II co-localized in the cell membrane region after EGF treatment. Our findings indicate that Annexin II is binding partner of SHP2 and the binding of SHP2 with Annexin II is affected by EGF stimulation, extracellular calcium levels, and the levels of HSP70.
Yoo
Jae Cheal
JC
Department of Molecular Genetics and Microbiology, State University of New York at Stony Brook, Stony Brook, NY 11794-5222, USA.
Hayman
Michael J
MJ
D000818:Animals; D017306:Annexin A2 / Q000378:metabolism*; D019556:COS Cells; D002118:Calcium / Q000378:metabolism*; D002522:Chlorocebus aethiops; D004815:Epidermal Growth Factor / Q000008:administration & dosage*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D011485:Protein Binding; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D017306:Annexin A2; D018840:HSP70 Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D004815:Epidermal Growth Factor; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases; D002118:Calcium