A role for Pyk2 and Src in linking G-protein-coupled receptors with MAP kinase activation

@article{Dikic1996ARF,
  title={A role for Pyk2 and Src in linking G-protein-coupled receptors with MAP kinase activation},
  author={Ivan Dikic and George Y. Tokiwa and Sima Lev and Sara A. Courtneidge and Joseph Schlessinger},
  journal={Nature},
  year={1996},
  volume={383},
  pages={547-550}
}
THE mechanisms by which mitogenic G-protein-coupled receptors activate the MAP kinase signalling pathway are poorly understood. Candidate protein tyrosine kinases that link G-protein-coupled receptors with MAP kinase include Src family kinases1, the epidermal growth factor receptor2, Lyn and Syk3. Here we show that lysophosphatidic acid (LPA) and bradykinin induce tyrosine phosphorylation of Pyk2 and complex formation between Pyk2 and activated Src. Moreover, tyrosine phosphorylation of Pyk2… 

Src and Pyk2 Mediate G-protein-coupled Receptor Activation of Epidermal Growth Factor Receptor (EGFR) but Are Not Required for Coupling to the Mitogen-activated Protein (MAP) Kinase Signaling Cascade*

It is shown that Src kinases are critical for activation of Pyk2 in response to GPCR-stimulation and thatPyk2 and Src are essential for GPCr-induced tyrosine phosphorylation of EGFR, and that Pyk1, Src, and SRC are dispensable for G PCR-induced activation of MAP kinase.

Adaptor Proteins Grb2 and Crk Couple Pyk2 with Activation of Specific Mitogen-activated Protein Kinase Cascades*

Evidence is provided that the protein tyrosine kinase Src and adaptor proteins Grb2, Crk, and p130Cas act as downstream mediators of Pyk2 leading to the activation of extracellular signal-regulated kinase (ERK) and c-Jun amino-terminal kinases (JNK).

Activation of Protein-tyrosine Kinase Pyk2 Is Downstream of Syk in FcεRI Signaling*

It is reported that Pyk2, another member of the focal adhesion kinase family, was present in the RBL-2H3 mast cell line and was rapidly tyrosine-phosphorylated and activated after FcεRI aggregation and may play a role in cell secretion.

Tyrosine kinases of the Src family participate in signaling to MAP kinase from both Gq and Gi-coupled receptors.

It is concluded that Src like kinase(s), acting downstream from beta gamma dimers, play an important role relaying signals from both Gq and Gi-coupled receptors to MAP kinase.

G Protein-coupled Receptors Mediate Two Functionally Distinct Pathways of Tyrosine Phosphorylation in Rat 1a Fibroblasts

It is proposed that an additional step involving vesicle-mediated endocytosis is required for the rapid, Ras-dependent activation of Erk kinases in fibroblasts.

Activation of protein tyrosine kinase PYK2 by the m1 muscarinic acetylcholine receptor.

PYK2 is established as an effector of the m1 muscarinic receptor in the regulation of multiple cell functions and specifically phosphorylates the carboxyl-terminal cytosolic portion of the potassium channel Kv1.2 in a manner regulated by them1 receptor.

The Transactivated Epidermal Growth Factor Receptor Recruits Pyk2 to Regulate Src Kinase Activity*

Reconstitution of the signaling molecules in HEK293 or vascular smooth muscle cells and subsequent determination of the EGF-induced Src kinase activity applying fluorescent sensor proteins demonstrated that a Ca2+-independent mode of Pyk2 activation is critical for the activation of Src downstream of the transactivated EGF receptor.

Gbetagamma subunits mediate Src-dependent phosphorylation of the epidermal growth factor receptor. A scaffold for G protein-coupled receptor-mediated Ras activation.

Data suggest that Gbetagamma subunit-mediated activation of Src family nonreceptor tyrosine kinases can account for the Gi-coupled receptor-mediated tyosine phosphorylation events that direct recruitment of the Shc and Grb2 adapter proteins to the membrane.

Src Homology 3 Binding Sites in the P2Y2 Nucleotide Receptor Interact with Src and Regulate Activities of Src, Proline-rich Tyrosine Kinase 2, and Growth Factor Receptors*

Dual immunofluorescence labeling of the P2Y2 receptor and the EGFR indicated that UTP caused an increase in the co-localization of these receptors in the plasma membrane that was prevented by the Src inhibitor PP2.

Related Adhesion Focal Tyrosine Kinase and the Epidermal Growth Factor Receptor Mediate the Stimulation of Mitogen-activated Protein Kinase by the G-protein-coupled P2Y2 Receptor

  • S. Soltoff
  • Biology, Computer Science
    The Journal of Biological Chemistry
  • 1998
The results demonstrate that the P2Y2 receptor-mediated transactivation of the EGF receptor occurs at a point downstream of RAFTK and indicate that the E GF receptor is required for P2 Y2 receptors-mediated MAP kinase activation.
...

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