doi:10.1093/jmcb/mju009
Journal of Molecular Cell Biology (2014), 6, 103
| 103
Editorial
New insights into cell signaling
C
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China E-mail: [email protected]
Their works revealed the molecular mechanism by which RIAM mediates Rap1-induced integrin activation. Previous studies have showed that the assembly and trafficking of the P2X3 receptor are important for its function of sensory processing and transmission in primary sensory neurons. In this issue, Dr Bao’s laboratory showed that a, b-MeATP significantly facilitated membrane delivery of the P2X3 receptor both in HEK293T cells over-expressing P2X3 receptor and in rat primary sensory neurons, which resulted in P2X3 receptor-mediated Ca2+ influx and activated Ca2+/ calmodulin-dependent protein kinase IIa (CaMKIIa). The authors further showed that increased P2X3 receptors on the cell membrane could promote P2X3 receptor-mediated signal transduction. The RIG-I-like receptors (RLRs), including RIG-I and MDA5, play pivotal roles in innate antiviral response. It was reported last year by Dr Shu’s group that the ribonucleoprotein PTB-binding 1 (RAVER1) as a specific MDA5-interacting protein could regulate activity of MDA5 but not RIG-I (Chen et al., 2013). In this issue, they showed that a TRIM family protein TRIM4 upregulated RIG-I-mediated IFN induction via associating with RIG-I for K63-linked polyubiquitination of RIG-I. Their findings suggest that RAVER1 and TRIM4 are responsible for differential regulation of MDA5- and RIG-Imediated innate antiviral response.
References Chen, H., Li, Y., Zhang, J., et al. (2013). RAVER1 is a coactivator of MDA5-mediated cellular antiviral response. J. Mol. Cell Biol. 5, 111 – 119. Wu, J. (2013). Cell signaling for pathological responses. J. Mol. Cell Biol. 5, 357.
# The Author (2014). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.
Downloaded from http://jmcb.oxfordjournals.org/ at Universitat de Girona on March 27, 2015
Editor-in-Chief Jiarui Wu
ell signaling has been well recognized as a highly complex process, which mainly delivers environmental information into cells. A number of regulating mechanisms of cell signaling have been uncovered in great details. Recently, JMCB also published several articles on new members or regulating mechanisms of various cell signaling pathways (Wu, 2013). In this issue, the collection of four articles will add new aspects to understanding the molecular mechanisms of cell signaling. It has been revealed that tyrosine kinase receptor vascular endothelial growth factor receptor 2 (VEGFR2) plays an important role in the regulation of angiogenesis. In the first article of this issue, Dr Giacca’s group identified that VEGFR2 of endothelial cells was acetylated at multiple lysine residues. These acetylations were under the reversible control by an acetyltransferase p300 and two deacetylases HDAC5 and HDAC6. The authors further showed that VEGFR2 acetylation significantly altered the kinetics of VEGFR2 phosphorylation after ligand binding, thus was required for the regulation of receptor phosphorylation. Their findings indicate that the acetylation involves in the control of VEGFR2 activity. Studies in Dr Wu’s laboratory determined the crystal structure of an active GTPase domain of the small GTPase Rap1 in complex with the Ras association (RA)–pleckstrin homology (PH) structural module of Rap1-interacting adaptor molecule (RIAM). The authors reported that several side chains of Rap1 were critical in determining the recognition of RIAM. They also showed that disruption of these side-chain interactions reduced the Rap1:RIAM association and resulted in a loss of co-clustering and cell adhesion.
Journal of Molecular Cell Biology (2014), 6, 103
| 103
Editorial
New insights into cell signaling
C
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China E-mail: [email protected]
Their works revealed the molecular mechanism by which RIAM mediates Rap1-induced integrin activation. Previous studies have showed that the assembly and trafficking of the P2X3 receptor are important for its function of sensory processing and transmission in primary sensory neurons. In this issue, Dr Bao’s laboratory showed that a, b-MeATP significantly facilitated membrane delivery of the P2X3 receptor both in HEK293T cells over-expressing P2X3 receptor and in rat primary sensory neurons, which resulted in P2X3 receptor-mediated Ca2+ influx and activated Ca2+/ calmodulin-dependent protein kinase IIa (CaMKIIa). The authors further showed that increased P2X3 receptors on the cell membrane could promote P2X3 receptor-mediated signal transduction. The RIG-I-like receptors (RLRs), including RIG-I and MDA5, play pivotal roles in innate antiviral response. It was reported last year by Dr Shu’s group that the ribonucleoprotein PTB-binding 1 (RAVER1) as a specific MDA5-interacting protein could regulate activity of MDA5 but not RIG-I (Chen et al., 2013). In this issue, they showed that a TRIM family protein TRIM4 upregulated RIG-I-mediated IFN induction via associating with RIG-I for K63-linked polyubiquitination of RIG-I. Their findings suggest that RAVER1 and TRIM4 are responsible for differential regulation of MDA5- and RIG-Imediated innate antiviral response.
References Chen, H., Li, Y., Zhang, J., et al. (2013). RAVER1 is a coactivator of MDA5-mediated cellular antiviral response. J. Mol. Cell Biol. 5, 111 – 119. Wu, J. (2013). Cell signaling for pathological responses. J. Mol. Cell Biol. 5, 357.
# The Author (2014). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.
Downloaded from http://jmcb.oxfordjournals.org/ at Universitat de Girona on March 27, 2015
Editor-in-Chief Jiarui Wu
ell signaling has been well recognized as a highly complex process, which mainly delivers environmental information into cells. A number of regulating mechanisms of cell signaling have been uncovered in great details. Recently, JMCB also published several articles on new members or regulating mechanisms of various cell signaling pathways (Wu, 2013). In this issue, the collection of four articles will add new aspects to understanding the molecular mechanisms of cell signaling. It has been revealed that tyrosine kinase receptor vascular endothelial growth factor receptor 2 (VEGFR2) plays an important role in the regulation of angiogenesis. In the first article of this issue, Dr Giacca’s group identified that VEGFR2 of endothelial cells was acetylated at multiple lysine residues. These acetylations were under the reversible control by an acetyltransferase p300 and two deacetylases HDAC5 and HDAC6. The authors further showed that VEGFR2 acetylation significantly altered the kinetics of VEGFR2 phosphorylation after ligand binding, thus was required for the regulation of receptor phosphorylation. Their findings indicate that the acetylation involves in the control of VEGFR2 activity. Studies in Dr Wu’s laboratory determined the crystal structure of an active GTPase domain of the small GTPase Rap1 in complex with the Ras association (RA)–pleckstrin homology (PH) structural module of Rap1-interacting adaptor molecule (RIAM). The authors reported that several side chains of Rap1 were critical in determining the recognition of RIAM. They also showed that disruption of these side-chain interactions reduced the Rap1:RIAM association and resulted in a loss of co-clustering and cell adhesion.
