Angiotensin II initiates tyrosine kinase Pyk2-dependent signalings leading to activation of Rac1-mediated c-Jun NH2-terminal kinase

Murasawa, Satoshi; Matsubara, Hiroaki; Mori, Yoshihide; Masaki, Hiroya; Shibasaki, Yasunobu; Kitabayashi, Issay; Tanaka, Yasuaki; Fujiyama, Sohichiro; Koyama, Yohko; Fujiyama, Atsuko; Iba, Satoshi; Iwasaka, Toshiji

doi:10.1074/jbc.m909999199

Cited by 34 publications

(40 citation statements)

References 48 publications

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“…3,5 PYK2 has been shown to mediate ERK and JNK activation by Ang II. 16,17 In contrast, we have reported that EGFR transactivation specifically mediates ERK and p38 MAPK activation by Ang II in VSMCs. 14 Based on this previous background, we have examined whether Rho/ROCK activation requires PYK2 or EGFR activation.…”

Section: Pyk2 and Pdz-rhogef Exist Upstream Of Rho/rock Activation Bymentioning

confidence: 84%

Signal-Crosstalk Between Rho/ROCK and c-Jun NH ₂ -Terminal Kinase Mediates Migration of Vascular Smooth Muscle Cells Stimulated by Angiotensin II

Ohtsu

Mifune

Frank

et al. 2005

ATVB

113

105

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Background-Rho and its effector Rho-kinase/ROCK mediate cytoskeletal reorganization as well as smooth muscle contraction. Recent studies indicate that Rho and ROCK are critically involved in vascular remodeling. Here, we tested the hypothesis that Rho/ROCK are critically involved in angiotensin II (Ang II)-induced migration of vascular smooth muscle cells (VSMCs) by mediating a specific signal cross-talk. Methods and Results-Immunoblotting demonstrated that Ang II stimulated phosphorylation of a ROCK substrate, regulatory myosin phosphatase targeting subunit (MYPT)-1. Phosphorylation of MYPT-1 as well as migration of VSMCs induced by Ang II was inhibited by dominant-negative Rho (dnRho) or ROCK inhibitor, Y27632. Ang II-induced c-Jun NH 2 -terminal kinase (JNK) activation, but extracellular signal-regulated kinase (ERK) activation was not mediated through Rho/ROCK. Thus, infection of adenovirus encoding dnJNK inhibited VSMC migration by Ang II. We have further demonstrated that the Rho/ROCK activation by Ang II requires protein kinase C-␦ (PKC␦) and proline-rich tyrosine kinase 2 (PYK2) activation, but not epidermal growth factor receptor transactivation. Also, VSMCs express PDZ-Rho guanine nucleotide exchange factor (GEF) and Ang II stimulated PYK2 association with tyrosine phosphorylated PDZ-RhoGEF. A ngiotensin II (Ang II) has been implicated in various cardiovascular diseases such as hypertension, atherosclerosis, and restenosis after angioplasty. 1 Therefore, there has been considerable interest in defining the functional significance of signaling pathways of the Ang II type 1 receptor (AT 1 ), which is dominantly expressed in vascular smooth muscle cells (VSMCs). 1-3 Through this receptor, Ang II stimulates hypertrophy and hyperplasia of VSMCs. 2 The AT 1 receptor primarily couples to G q leading to elevation of intracellular Ca 2ϩ and activation of protein kinase C (PKC). 2 In addition, tyrosine kinase activation by Ang II is linked to downstream mitogenactivated protein kinase (MAPK) activation, thereby mediating the growth promoting response in VSMCs. 2,4,5 In this regard, several key tyrosine kinases have been identified that may contribute to the growth-promoting effects of the AT 1 receptor. These kinases include epidermal growth factor receptor (EGFR) and proline-rich tyrosine kinse 2 (PYK2). 4,5 In addition to its growth responses, VSMC migration by Ang II is strongly implicated in various cardiovascular diseases, 6 whereas the detailed signaling mechanisms by which the AT 1 receptor mediates migration are insufficiently characterized. At least, a MAPK, ERK appears to be required for Ang II-induced migration of VSMCs. 7 Recently, Zahn et al showed that 3 major MAPKs, ERK, p38MAPK, and c-Jun NH 2 -terminal kinase (JNK), are all required for VSMC migration induced by platelet-derived growth factor (PDGF), 8 suggesting that these MAPKs coordinately mediate VSMC migration. A small G protein, Rho, and its effector Rho-kinase/ ROCK, are involved in many aspects of cell motility, from smooth muscle...

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Section: Pyk2 and Pdz-rhogef Exist Upstream Of Rho/rock Activation Bymentioning

confidence: 84%

Signal-Crosstalk Between Rho/ROCK and c-Jun NH ₂ -Terminal Kinase Mediates Migration of Vascular Smooth Muscle Cells Stimulated by Angiotensin II

Ohtsu

Mifune

Frank

et al. 2005

ATVB

113

105

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“…Similar to Src kinases, Pyk2 may exert diverse biological functions depending on its restricted expression and the activating receptor or stimulus (Lev et al 1995, Dikic et al 1996, Della Rocca et al 1999. Very recently, Pyk2 was shown as a potent mediator of ATII-induced c-Jun NH2-terminal (Jnk) kinase activation and c-jun gene expression (Murasawa et al 2000), a process distinct from EGFR and Ras activation which mediate ATII-induced Erk induction (Eguchi et al 1998, Murasawa et al 1998). …”

Section: Involvement Of Calcium and Pyk2mentioning

confidence: 99%

The epidermal growth factor receptor family as a central element for cellular signal transduction and diversification.

Prenzel¹,

Fischer²,

Streit³

et al. 2001

Endocrine-Related Cancer

595

471

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Homeostasis of multicellular organisms is critically dependent on the correct interpretation of the plethora of signals which cells are exposed to during their lifespan. Various soluble factors regulate the activation state of cellular receptors which are coupled to a complex signal transduction network that ultimately generates signals defining the required biological response. The epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases represents both key regulators of normal cellular development as well as critical players in a variety of pathophysiological phenomena. The aim of this review is to give a broad overview of signal transduction networks that are controlled by the EGFR superfamily of receptors in health and disease and its application for target-selective therapeutic intervention. Since the EGFR and HER2 were recently identified as critical players in the transduction of signals by a variety of cell surface receptors, such as G-protein-coupled receptors and integrins, our special focus is the mechanisms and significance of the interconnectivity between heterologous signalling systems.

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“…These second messengers, in turn, mobilize Ca 2ϩ from intracellular stores and activate PKC, respectively. Previous studies have shown Pyk2 activation in response to a variety of stimuli to be dependent on PKC and Ca 2ϩ release (36,58) or on Ca 2ϩ release alone (12,29,37). To study the postreceptor regulation of Pyk2 in IEC-18 cells, we first examined the role of the PLC pathway, focusing on the effects of PKC activation and Ca 2ϩ release.…”

Section: Ang II and Lpa Induce Pyk2 Tyrosine Phosphorylation In Iecmentioning

confidence: 99%

“…These agonists are known to promote G␣ q -mediated activation of phospholipase C (PLC), generating second messengers that mobilize Ca 2ϩ and activate PKC, which in turn induce Pyk2 tyrosine phosphorylation and activation. However, the relative contributions of Ca 2ϩ mobilization and PKC to Pyk2 activation vary widely among different agonists and cell types (12,25,29,36,58). The role of these signaling pathways in the regulation of Pyk2 tyrosine phosphorylation has not been studied in normal IEC.…”

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confidence: 99%

ANG II and LPA induce Pyk2 tyrosine phosphorylation in intestinal epithelial cells: role of Ca²⁺, PKC, and Rho kinase

Wu¹,

Chiu

Rozengurt

2002

American Journal of Physiology-Cell Physiology

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2001.-The G protein-coupled receptor agonists angiotensin II (ANG II) and lysophosphatidic acid (LPA) rapidly induce tyrosine phosphorylation of the cytosolic proline-rich tyrosine kinase 2 (Pyk2) in IEC-18 intestinal epithelial cells. The combined Pyk2 tyrosine phosphorylation induced by phorbol 12,13-dibutyrate, a direct agonist of protein kinase C (PKC), and ionomycin, a Ca 2ϩ ionophore, was equal to that induced by ANG II. Inhibition of either PKC or Ca 2ϩ signaling attenuated the effect of ANG II and LPA, although simultaneous inhibition of both pathways failed to completely abolish Pyk2 tyrosine phosphorylation. Cytochalasin D, which disrupts stress fibers, strongly inhibited the response of Pyk2 to ANG II or LPA. The distinct Rho-associated kinase (ROK) inhibitors HA-1077 and Y-27632, as well as the Rho inhibitor Clostridium botulinum C3 exoenzyme, also significantly attenuated ANG II-and LPA-stimulated Pyk2 tyrosine phosphorylation. Simultaneous inhibition of PKC, Ca 2ϩ , and either actin assembly or ROK completely abolished the Pyk2 response. Together, these results show that ANG II and LPA rapidly induce Pyk2 tyrosine phosphorylation in intestinal epithelial cells via separate Ca 2ϩ -, PKC-, and Rho-mediated pathways.

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Angiotensin II initiates tyrosine kinase Pyk2-dependent signalings leading to activation of Rac1-mediated c-Jun NH2-terminal kinase

Cited by 34 publications

References 48 publications

Signal-Crosstalk Between Rho/ROCK and c-Jun NH ₂ -Terminal Kinase Mediates Migration of Vascular Smooth Muscle Cells Stimulated by Angiotensin II

Signal-Crosstalk Between Rho/ROCK and c-Jun NH ₂ -Terminal Kinase Mediates Migration of Vascular Smooth Muscle Cells Stimulated by Angiotensin II

The epidermal growth factor receptor family as a central element for cellular signal transduction and diversification.

ANG II and LPA induce Pyk2 tyrosine phosphorylation in intestinal epithelial cells: role of Ca²⁺, PKC, and Rho kinase

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Angiotensin II initiates tyrosine kinase Pyk2-dependent signalings leading to activation of Rac1-mediated c-Jun NH2-terminal kinase

Cited by 34 publications

References 48 publications

Signal-Crosstalk Between Rho/ROCK and c-Jun NH 2 -Terminal Kinase Mediates Migration of Vascular Smooth Muscle Cells Stimulated by Angiotensin II

Signal-Crosstalk Between Rho/ROCK and c-Jun NH 2 -Terminal Kinase Mediates Migration of Vascular Smooth Muscle Cells Stimulated by Angiotensin II

The epidermal growth factor receptor family as a central element for cellular signal transduction and diversification.

ANG II and LPA induce Pyk2 tyrosine phosphorylation in intestinal epithelial cells: role of Ca2+, PKC, and Rho kinase

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Signal-Crosstalk Between Rho/ROCK and c-Jun NH ₂ -Terminal Kinase Mediates Migration of Vascular Smooth Muscle Cells Stimulated by Angiotensin II

Signal-Crosstalk Between Rho/ROCK and c-Jun NH ₂ -Terminal Kinase Mediates Migration of Vascular Smooth Muscle Cells Stimulated by Angiotensin II

ANG II and LPA induce Pyk2 tyrosine phosphorylation in intestinal epithelial cells: role of Ca²⁺, PKC, and Rho kinase