G13α-mediated PYK2 Activation

Shi, Chong-Shan; Sinnarajah, Srikumar; Cho, Hyeseon; Kozasa, Tohru; Kehrl, John H.

doi:10.1074/jbc.m908449199

Cited by 81 publications

(37 citation statements)

References 32 publications

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“…On the other hand, Rho could also influence Pyk2 via the PLC pathway, since it promotes resynthesis of PtdIns(4,5)P 2 , the major substrate for PLC (45). The effect of the Rho pathway on Pyk2 is not well described, although a recent report has implicated G 12/13 -mediated Rho activation as being dependent on, but not upstream of, Pyk2 (50).…”

Section: Ang Ii-or Lpa-induced Pyk2 Tyrosine Phosphorylation Is Inhibmentioning

confidence: 93%

“…Tyr-402, the major site of Pyk2 autophosphorylation upon activation, provides a potential high-affinity binding site for SH2 domains of Src family kinases (14) and is essential for the induction of Pyk2 kinase activity (5). In turn, Src kinases bound at Tyr-402 are able to transphosphorylate Pyk2 at additional sites, including Tyr-580 within the kinase domain, which appears to further enhance Pyk2 kinase activity (27,50). Parallel cultures of IEC-18 cells were stimulated with ANG II or LPA, and the whole cell lysates were separated by SDS-PAGE, followed by Western blotting with Pyk2 antibodies specific for the phosphorylated Tyr-402 (Fig.…”

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

confidence: 99%

“…Pyk2 lacks Src homology 2 and 3 (SH2 and SH3) domains but contains sequences capable of binding to SH2 and SH3 domains of other proteins, including Src family kinases, the adaptor protein Grb2 (14,26), and the focal adhesion proteins paxillin (17,19,22,28,46) and p130CAS (43). In particular, tyrosine-402 (Tyr-402) has been identified as the key site for Pyk2 autophosphorylation and activation (14), with other tyrosine sites contributing to subsequent transphosphorylation and enhanced kinase activity (27,50). Pyk2 has been found to localize to focal adhesions in response to cell stimulation or extracellular matrix attachment (30).…”

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confidence: 99%

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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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Section: Ang Ii-or Lpa-induced Pyk2 Tyrosine Phosphorylation Is Inhibmentioning

confidence: 93%

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

confidence: 99%

mentioning

confidence: 99%

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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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“…For the latter, we took advantage of the observation that RGL-containing RhoGEFs activate the transcriptional activity of the c-fos SRE (Fukuhara et al, 1999;Shi et al, 2000). Indeed, all three members of this GEF family stimulated luciferase expression from the SRE Figure 4 Homo-and hetero-oligomerization of RGL-containing RhoGEFs.…”

Section: Regulation Of Rgl-containing Rhogefs H Chikumi Et Almentioning

confidence: 99%

Homo- and hetero-oligomerization of PDZ-RhoGEF, LARG and p115RhoGEF by their C-terminal region regulates their in vivo Rho GEF activity and transforming potential

et al. 2004

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PDZ-RhoGEF, LARG, and p115RhoGEF are members of a newly identified family of Rho-guanine nucleotide exchange factors (GEFs) exhibiting a unique structural feature consisting of the presence of an area of similarity to regulators of G protein signaling (RGS). This RGS-like (RGL) domain provides a functional motif by which Ga 12 and Ga 13 can bind and regulate the activity of these RhoGEFs, thus providing a direct link from these heterotrimeric G proteins to Rho. PDZ-RhoGEF and LARG can also be phosphorylated by tyrosine kinases, including FAK, and associate with Plexin B, a semaphorin receptor, which controls axon guidance during development, through their PDZ domain, thereby stimulating Rho. Interestingly, while characterizing a PDZ-RhoGEF antiserum, we found that a transfected PDZ-RhoGEF construct associated with the endogenous PDZ-RhoGEF. Indeed, we observed that PDZ-RhoGEF and LARG can form homo-and hetero-oligomers, whereas p115RhoGEF can only homo-oligomerize, and that this intermolecular interaction was mediated by their unique C-terminal regions. Deletion of the C-terminal tail of PDZ-RhoGEF had no significant effect on the GEF catalytic activity towards Rho in vitro, but resulted in a drastic increase in the ability to stimulate a serum response element reporter and the accumulation of the GTP-bound Rho in vivo. Furthermore, removal of the C-termini of each of the three RGL-containing GEFs unleashed their full transforming potential. Together, these findings suggest the existence of a novel mechanism controlling the activity of PDZRhoGEF, LARG, and p115RhoGEF, which involves homo-and hetero-oligomerization through their inhibitory C-terminal region.

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“…For example, CrkL, a gene highly homologous to the oncogene adaptor Crk, associates with GCKR (also referred to as KHS1) in the cytoplasm through its SH3 motif to activate the SAPK/JNK pathway (Shi et al, 2000). Additionally however, CrkL functions as a nuclear adaptor and transcriptional activator in Bcr-Abl expressing cells (Rhodes et al, 2000).…”

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confidence: 99%

HACS1 encodes a novel SH3-SAM adaptor protein differentially expressed in normal and malignant hematopoietic cells

et al. 2001

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SH3 and SAM domains are protein interaction motifs that are predominantly seen in signaling molecules, adaptors, and sca old proteins. We have identi®ed a novel family of putative adaptor genes that includes HACS1. HACS1 encodes a 441 amino acid protein that is di erentially expressed in hematopoietic cells and has restricted expression in human tissues. Its SH3 domain is most similar to the same motif in Crk and its SAM domain shares homology with a family of uncharacterized putative sca old and adaptor proteins. HACS1 maps to human chromosome 21q11.2 in a region that is frequently disrupted by translocation events in hematopoietic malignancies. Polyclonal antibodies against HACS1 recognized a 49.5 kDa protein whose mRNA is expressed in human immune tissues, bone marrow, heart, lung, placenta and brain. Cell lines and primary cells from acute myeloid leukemias and multiple myeloma patients express HACS1. Immunostaining and cellular fractionation studies localized the HACS1 protein predominantly to the cytoplasm. Oncogene (2001) 20, 5373 ± 5377.

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G13α-mediated PYK2 Activation

Cited by 81 publications

References 32 publications

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

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

Homo- and hetero-oligomerization of PDZ-RhoGEF, LARG and p115RhoGEF by their C-terminal region regulates their in vivo Rho GEF activity and transforming potential

HACS1 encodes a novel SH3-SAM adaptor protein differentially expressed in normal and malignant hematopoietic cells

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G13α-mediated PYK2 Activation

Cited by 81 publications

References 32 publications

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

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

Homo- and hetero-oligomerization of PDZ-RhoGEF, LARG and p115RhoGEF by their C-terminal region regulates their in vivo Rho GEF activity and transforming potential

HACS1 encodes a novel SH3-SAM adaptor protein differentially expressed in normal and malignant hematopoietic cells

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

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