Angiotensin IV induces tyrosine phosphorylation of focal adhesion kinase and paxillin in proximal tubule cells.

Chen JK, Zimpelmann J, Harris RC, Burns KD
Am J Physiol Renal Physiol. 2001 280 (6): F980-8

PMID: 11352837 · DOI:10.1152/ajprenal.2001.280.6.F980

Angiotensin IV (ANG IV), the COOH-terminal hexapeptide fragment of angiotensin II (ANG II), binds to specific sites in the kidney, distinct from type 1 (AT(1)) and type 2 (AT(2)) receptors and designated type 4 (AT(4)) receptors. We determined signaling pathways for ANG IV in a proximal tubular cell line, LLC-PK(1)/Cl(4). In these cells, we found no specific binding of [(125)I]-ANG II. In contrast, ANG IV dose dependently competed for [(125)I]-labeled ANG IV binding, with no displacement by either ANG II, the AT(1) receptor antagonist losartan, or the AT(2) antagonist PD-123319. Saturation binding indicated the presence of AT(4) receptors of high affinity [dissociation constant (K(d)) = 1.4 nM]. ANG IV did not affect cAMP or cGMP production and did not increase cytosolic calcium concentration in these cells. In contrast, immunoprecipitation and immunoblotting studies revealed that ANG IV caused dose-dependent tyrosine phosphorylation of p125-focal adhesion kinase (p125-FAK) and p68-paxillin within 2 min, with maximal stimulation at 30 min. ANG IV-stimulated tyrosine phosphorylation of p125-FAK and paxillin was not affected by pretreatment with either losartan or PD-123319, and ANG II (10(-7) M) did not induce protein tyrosine phosphorylation. Our results indicate that LLC-PK(1)/Cl(4) cells express ANG IV receptors, which we demonstrate for the first time are linked to tyrosine phosphorylation of focal adhesion-associated proteins. This suggests that ANG IV, a product of ANG II metabolism, may regulate function of the focal adhesion complex in proximal tubule cells.

MeSH Terms (22)

Angiotensin II Animals Binding, Competitive Calcium Cyclic AMP Cyclic GMP Cytoskeletal Proteins Dose-Response Relationship, Drug Focal Adhesion Protein-Tyrosine Kinases Iodine Radioisotopes Kidney Tubules, Proximal LLC-PK1 Cells Paxillin Phosphoproteins Phosphorylation Protein-Tyrosine Kinases Renin-Angiotensin System Signal Transduction Swine Thymidine Tritium Tyrosine

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