Tyrosine kinase Pyk2 mediates G-protein-coupled receptor regulation of the Ewing sarcoma RNA-binding protein EWS

  title={Tyrosine kinase Pyk2 mediates G-protein-coupled receptor regulation of the Ewing sarcoma RNA-binding protein EWS},
  author={Jason S. Felsch and William Arbuthnot Sir Lane and Ernest G. Peralta},
  journal={Current Biology},

Figures from this paper

Oncogenic serine-threonine kinase receptor-associated protein modulates the function of Ewing sarcoma protein through a novel mechanism.

This study provides a novel TGF-beta-independent function of STRAP and describes a mechanism by which STRAP regulates the function of oncogenic EWS protein.

The Ewing's sarcoma gene product functions as a transcriptional activator.

The nuclear Ewing's sarcoma proto-oncoprotein can function as a transcriptional cofactor in conjunction with CBP/p300, indicating that EWS-mediated gene regulation depends on CBP or p300.

Analysis of Ewing sarcoma (EWS)-binding proteins: interaction with hnRNP M, U, and RNA-helicases p68/72 within protein-RNA complexes.

It is shown that methylation of recombinant E WS protein in HEK cells occurs immediately after or even during translation, and a role of EWS protein methylation in RNA-binding and affecting the activation/repression activity or even in the stabilization of the EWSprotein seems very likely.

EWS represses cofilin 1 expression by inducing nuclear retention of cofilin 1 mRNA

Overexpression of full-length EWS repressed protein expression and induced nuclear retention of reporter mRNAs in a tethering assay and suggested that CFL1 promotes development of ESFT, suggesting that targeting CFL1 might provide another novel approach for treatment of this aggressive disease.

A repetitive element containing a critical tyrosine residue is required for transcriptional activation by the EWS/ATF1 oncogene

In the context of EWS/ATF1, the EFP that causes malignant melanoma of soft parts, trans-cooperation by small regions of the EAD results in potent transcriptional activation dependent on the conserved tyrosine residues present in DHRs.

RGG-boxes of the EWS oncoprotein repress a range of transcriptional activation domains

It is proposed that a key function of RGG boxes within native EWS is to restrict promiscuous activation by the EAD while still allowing EWS to enter functional transcription complexes and participate in other transactions involving pre-mRNAs.



The Prooncoprotein EWS Binds Calmodulin and Is Phosphorylated by Protein Kinase C through an IQ Domain*

It is reported that EWS, a nuclear RNA-binding prooncoprotein, contains an IQ domain, is phosphorylated by protein kinase C, and interacts with calmodulin, and that IQ domains may provide a regulatory link between Ca2+ signal transduction pathways and RNA processing.

EWS, but Not EWS-FLI-1, Is Associated with Both TFIID and RNA Polymerase II: Interactions between Two Members of the TET Family, EWS and hTAFII68, and Subunits of TFIID and RNA Polymerase II Complexes

It is demonstrated that a portion of EWS is able to associate with the basal transcription factor TFIID, which is composed of the TATA-binding protein (TBP) and TBP-associated factors (TAFIIs) and subunits of Pol II have been identified, confirming the association with the polymerase.

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.

Activation of a Novel Calcium-dependent Protein-tyrosine Kinase

In summary, cells expressing CADTK/PYK2 appear to have two alternative JNK activation pathways: one stress-activated and the other calcium-dependent.

Identification of the binding site for Gqalpha on its effector Bruton's tyrosine kinase.

  • Y. C. MaX. Huang
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1998
This work demonstrates that G protein Gqalpha binds directly to the nonreceptor Bruton's tyrosine kinase (Btk) to a region composed of a Tec-homology (TH) domain and a sarcoma virus tyrosinesine kinases (Src)-homology 3 (SH3) domain both in vitro and in vivo.

The SH3 Domain of Bruton's Tyrosine Kinase Interacts with Vav, Sam68 and EWS

The authors show that a Pro → Leu substitution in a region of the SH3 domain, which is deleted in an XLA patient, is sufficient to abolish BTK‐SH3 binding potential and several of the BTK'S3 binding proteins, including Sam68, EWS and Vav are tyrosine phosphorylated in conditions that also promote BTK kinase activity.

Characterization of RAFTK, a novel focal adhesion kinase, and its integrin-dependent phosphorylation and activation in megakaryocytes.

The biochemical characterization and functional analysis of the RAFTK protein suggest that it is a novel member of the FAK family, that it localizes to focal adhesion-like structures in CMK megakaryocytic cells, and that it participates in integrinmediated signaling pathways inmegakaryocytes.

Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours

Phylogenetically conserved restriction fragments in the vicinity of EWSR1 and EWSR2, the genomic regions where the breakpoints of chromosome 22 and chromosome 11 are, respectively, have allowed identification of transcribed sequences from these regions and has indicated that a hybrid transcript might be generated by the translocation.

Combinatorial generation of variable fusion proteins in the Ewing family of tumours.

In Ewing's sarcoma and malignant melanoma of soft parts, translocations of band 22q12 to chromosome 11 and 12 result in the fusion of EWS with the transcription factors FLI‐1 and ATF1, respectively, suggesting that oncogenic conversion is achieved by the linking of the two domains with no marked constraint on the connecting peptide.

Human N-Myristoyltransferase Amino-terminal Domain Involved in Targeting the Enzyme to the Ribosomal Subcellular Fraction*

In vivo and in vitrosubcellular targeting and recombinant expression experiments identify a native hNMT that is 10–12 kDa larger than the enzyme predicted by the originally assigned hN MT gene and which is apparently translated from an alternative up-stream start site.