EGF and dextran-conjugated EGF induces differential phosphorylation of the EGF receptor.
Dextran-conjugated EGF (EGF-dextran) has a potential use for targeted radionuclide therapy of tumors that overexpress the epidermal growth factor receptor (EGFR). There are plans to treat both bladder carcinomas and malignant gliomas with local injections of radiolabeled EGF-dextran since these tumors often express high levels of EGFR. In this report we show that EGF and EGF-dextran differentially activate the EGFR. In the human glioma cell line U-343, activation of the serine/threonine kinases Erk and Akt is identical upon stimulation with EGF or EGF-dextran. However, the effect on phospholipase Cgamma1 (PLCgamma1) phosphorylation differs. In cells stimulated with EGF-dextran, the PLCgamma1 phosphorylation is lower than in cells stimulated with EGF. This observation could be explained by the fact that the PLCgamma1 association sites in the EGFR, tyrosine residues 992 and 1173, were phosphorylated to a lower degree when the receptor was stimulated with EGF-dextran as compared to with EGF.
Hägg
Maria
M
Ludwig Institute for Cancer Research, Biomedical Center, SE-751 24 Uppsala, Sweden.
Liljegren
Asa
A
Carlsson
Jörgen
J
Rönnstrand
Lars
L
Lennartsson
Johan
J
D003911:Dextrans / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D051966:Phospholipase C gamma; D010766:Phosphorylation; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism; D014443:Tyrosine / Q000737:chemistry
D003911:Dextrans; D007527:Isoenzymes; C067291:epidermal growth factor-dextran conjugate; D014443:Tyrosine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D010738:Type C Phospholipases; D051966:Phospholipase C gamma