Inhibition of AT(1) receptor internalization by concanavalin A blocks angiotensin II-induced ERK activation in vascular smooth muscle cells - Involvement of epidermal growth factor receptor proteolysis but not AT(1) receptorinternalization
H. Tang et al., Inhibition of AT(1) receptor internalization by concanavalin A blocks angiotensin II-induced ERK activation in vascular smooth muscle cells - Involvement of epidermal growth factor receptor proteolysis but not AT(1) receptorinternalization, J BIOL CHEM, 275(18), 2000, pp. 13420-13426
Recent studies of beta(2)-adrenergic receptor suggest that agonist-promoted
receptor internalization may play an important role in extracellular signa
l-regulated kinase (ERK) activation by G protein-coupled receptors, In the
present study, we explored the effects of angiotensin II (Ang II) type-1 re
ceptor (AT(1)) internalization on Ang II-induced activation of ERK using th
e receptor internalization blocker concanavalin A (ConA) and the carboxyl t
erminus-truncated receptor mutants with impaired internalization. ConA inhi
bited AT(1) receptor internalization without affecting ligand binding to th
e receptor, Ang II-induced generation of second messengers, and activation
of tyrosine kinases Src and Pyk2 in vascular smooth muscle cells (VSMC), Co
nA blocked ERK activation evoked by Ang II and the calcium ionophore A23187
, Impairment of AT(1) receptor internalization by truncating the receptor c
arboxyl terminus did not affect Ang II-induced ERK activation. ConA induced
proteolytic cleavage of the epidermal growth factor (EGF) receptor at carb
oxyl terminus and abolished Ang II-induced transactivation of the EGF recep
tor, which is critical for ERR activation by Ang II in VSMC, ConA also indu
ced proteolysis of erbB-2 but not platelet-derived growth factor receptor.
Thus, ConA blocks Ang II-induced ERR activation in VSMC through a distinct
mechanism, the ConA-mediated proteolysis of the EGF receptor.