Protein kinase Cα activation by RET: evidence for a negative feedback mechanism controlling RET tyrosine kinase
作者： Francesco Andreozzi , Rosa Marina Melillo , Francesca Carlomagno , Francesco Oriente , Claudia Miele
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摘要: We have studied the role of protein kinase C (PKC) in signaling RET tyrosine receptor. By using a chimeric receptor (E/R) which can be tightly controlled by addition epidermal growth factor (EGF), we found that triggering induces strong increase PKCα, PKCδ and PKCζ activity not PKCζ, forms ligand-dependent complex with E/R. identified 1062 carboxyl-terminal tail as docking site for PKCα. Block PKC bisindolylmaleimide or chronic phorbol esters treatment decreased EGF-induced serine/threonine phosphorylation E/R, while it caused similarly sized E/R mitogenic signaling. Conversely, acute treatment, promotes activity, increased levels significantly its phosphotyrosine content. A threefold reduction constitutively active RET/MEN2A oncoprotein was observed upon coexpression conclude binds to activates turn, causes downregulates downstream signaling, thus functioning negative feedback loop modulate activity.
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