Effect of angiotensin II type 2 receptor on tyrosine kinase Pyk2 and c-Jun NH2-terminal kinase via SHP-1 tyrosine phosphatase activity: evidence from vascular-targeted transgenic mice of AT2 receptor.

Angiotensin II (Ang II) has two major receptor isoforms, AT1 and AT2. AT1 transphosphorylates Ca(2+)-sensitive tyrosine kinase Pyk2 to activate c-Jun NH2-terminal kinase (JNK). Although AT2 inactivates extracellular signal-regulated kinase (ERK) via tyrosine phosphatases (PTP), the action of AT2 on Pyk2 and JNK remains undefined. Using AT2-overexpressing vascular smooth muscle cells (AT2-VSMC) from AT2-transgenic mice, we studied these undefined actions of AT2. AT1-mediated JNK activity was increased 2.2-fold by AT2 inhibition, which was abolished by orthovanadate. AT2 did not affect AT1-mediated Pyk2 phosphorylation, but attenuated c-Jun mRNA accumulation by 32%. The activity of src-homology 2 domain-containing PTP (SHP-1) was significantly upregulated 1 min after AT2 stimulation. Stable overexpression of SHP-1 dominant negative mutant in AT2-VSMC completely abolished AT2-mediated inhibition of JNK activation and c-Jun expression. These findings suggest that AT2 inhibits JNK activity by affecting the downstream signal of Pyk2 in a SHP-1-dependent manner, leading to a decrease in c-Jun expression.

[1]  Y. Mori,et al.  Angiotensin II initiates tyrosine kinase Pyk2-dependent signalings leading to activation of Rac1-mediated c-Jun NH2-terminal kinase. , 2000, The Journal of biological chemistry.

[2]  R. Ganju,et al.  β-Chemokine Receptor CCR5 Signals through SHP1, SHP2, and Syk* , 2000, The Journal of Biological Chemistry.

[3]  A. Strosberg,et al.  Functional trans-inactivation of insulin receptor kinase by growth-inhibitory angiotensin II AT2 receptor. , 2000, Molecular endocrinology.

[4]  Z. Zhao,et al.  Regulation of Calcium-sensitive Tyrosine Kinase Pyk2 by Angiotensin II in Endothelial Cells , 2000, The Journal of Biological Chemistry.

[5]  Y. Mori,et al.  Angiotensin II type 2 receptor overexpression activates the vascular kinin system and causes vasodilation. , 1999, The Journal of clinical investigation.

[6]  L. Daviet,et al.  Analysis of functional domains of angiotensin II type 2 receptor involved in apoptosis. , 1999, Molecular endocrinology.

[7]  H. Matsubara,et al.  Pathophysiological role of angiotensin II type 2 receptor in cardiovascular and renal diseases. , 1998, Circulation research.

[8]  Y. Mori,et al.  Angiotensin II type 2 receptor is upregulated in human heart with interstitial fibrosis, and cardiac fibroblasts are the major cell type for its expression. , 1998, Circulation research.

[9]  Y. Mori,et al.  Role of calcium-sensitive tyrosine kinase Pyk2/CAKbeta/RAFTK in angiotensin II induced Ras/ERK signaling. , 1998, Hypertension.

[10]  A. Greene,et al.  Localization of the ANG II type 2 receptor in the microcirculation of skeletal muscle. , 1998, American journal of physiology. Heart and circulatory physiology.

[11]  M. Shibuya,et al.  Angiotensin II type 1 receptor-induced extracellular signal-regulated protein kinase activation is mediated by Ca2+/calmodulin-dependent transactivation of epidermal growth factor receptor. , 1998, Circulation research.

[12]  L. Graves,et al.  Angiotensin II stimulates ERK via two pathways in epithelial cells: protein kinase C suppresses a G–protein coupled receptor–EGF receptor transactivation pathway , 1998, The EMBO journal.

[13]  H. Kawakatsu,et al.  Calcium-dependent Epidermal Growth Factor Receptor Transactivation Mediates the Angiotensin II-induced Mitogen-activated Protein Kinase Activation in Vascular Smooth Muscle Cells* , 1998, The Journal of Biological Chemistry.

[14]  H. Matsubara,et al.  Molecular insights into angiotensin II type 1 and type 2 receptors: expression, signaling and physiological function and clinical application of its antagonists. , 1998, Endocrine journal.

[15]  M. Kasuga,et al.  Epidermal growth factor stimulates the tyrosine phosphorylation of SHPS-1 and association of SHPS-1 with SHP-2, a SH2 domain-containing protein tyrosine phosphatase. , 1997, Biochemical and biophysical research communications.

[16]  M. Horiuchi,et al.  Angiotensin Type 2 Receptor Dephosphorylates Bcl-2 by Activating Mitogen-activated Protein Kinase Phosphatase-1 and Induces Apoptosis* , 1997, The Journal of Biological Chemistry.

[17]  R. Carey,et al.  The subtype 2 (AT2) angiotensin receptor mediates renal production of nitric oxide in conscious rats. , 1997, The Journal of clinical investigation.

[18]  A. Strosberg,et al.  Angiotensin II type 2 receptors mediate inhibition of mitogen-activated protein kinase cascade and functional activation of SHP-1 tyrosine phosphatase. , 1997, The Biochemical journal.

[19]  R. Anderegg,et al.  Activation of a Novel Calcium-dependent Protein-tyrosine Kinase , 1996, The Journal of Biological Chemistry.

[20]  G. Booz,et al.  Role of type 1 and type 2 angiotensin receptors in angiotensin II-induced cardiomyocyte hypertrophy. , 1996, Hypertension.

[21]  T. Unger,et al.  The angiotensin II AT2 receptor inhibits proliferation and promotes differentiation in PC12W cells , 1996, Molecular and Cellular Endocrinology.

[22]  C. Sumners,et al.  Mitogen-activated Protein Kinases in Rat Brain Neuronal Cultures Are Activated by Angiotensin II Type 1 Receptors and Inhibited by Angiotensin II Type 2 Receptors* , 1996, The Journal of Biological Chemistry.

[23]  M. Horiuchi,et al.  Angiotensin II type 2 receptor mediates programmed cell death. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[24]  F. Gaits,et al.  Tyrosine phosphorylation of an SH2‐containing protein tyrosine phosphatase is coupled to platelet thrombin receptor via a pertussis toxin‐sensitive heterotrimeric G‐protein. , 1995, The EMBO journal.

[25]  Ursula Klingmüller,et al.  Specific recruitment of SH-PTP1 to the erythropoietin receptor causes inactivation of JAK2 and termination of proliferative signals , 1995, Cell.

[26]  M. Paul,et al.  The angiotensin AT2-receptor mediates inhibition of cell proliferation in coronary endothelial cells. , 1995, The Journal of clinical investigation.

[27]  C. Walsh,et al.  Intramolecular regulation of protein tyrosine phosphatase SH-PTP1: a new function for Src homology 2 domains. , 1994, Biochemistry.

[28]  D. Beier,et al.  Mutations at the murine motheaten locus are within the hematopoietic cell protein-tyrosine phosphatase (Hcph) gene , 1993, Cell.

[29]  T. Inagami,et al.  Angiotensin II Receptor: Molecular Cloning, Functions, and Regulation , 1994 .

[30]  G. Booz,et al.  Cardiac actions of angiotensin II: Role of an intracardiac renin-angiotensin system. , 1992, Annual review of physiology.