A5084599052- Microtubule and mitosis dynamics
- 14-3-3 protein interactions
- Axon Guidance and Neuronal Signaling
- ATP Synthase and ATPases Research
- Endoplasmic Reticulum Stress and Disease
- Hippo pathway signaling and YAP/TAZ
- Chromatography in Natural Products
- Ubiquitin and proteasome pathways
- Protein Tyrosine Phosphatases
- Zebrafish Biomedical Research Applications
- Cellular transport and secretion
- Pancreatic function and diabetes
Walter and Eliza Hall Institute of Medical Research
2021-2024
The University of Melbourne
2021-2023
Abstract PEAK pseudokinases regulate cell migration, invasion and proliferation by recruiting key signaling proteins to the cytoskeleton. Despite lacking catalytic activity, alteration in their expression level is associated with several aggressive cancers. Here, we elucidate molecular details of interactions adapter CrkII Grb2 scaffold protein 14-3-3. Our findings rationalize why dimerization has a crucial function signal transduction provide biophysical structural data unravel binding...
The pseudokinase scaffolds PEAK1 and PEAK2 are implicated in cancer cell migration metastasis. We characterized the regulation role of third family member PEAK3 signaling. Similar to PEAK2, formed both homotypic heterotypic complexes. In addition, like PEAK1, it bound adaptors Grb2 CrkII. However, unlike homodimerized also interacted with ARF GTPase-activating protein ASAP1, E3 ubiquitin ligase Cbl, kinase PYK2. Dimerization subsequent phosphorylation on Tyr 24 , likely by a Src kinase, were...
EphB6 and EphA10 are two poorly characterised pseudokinase members of the Eph receptor family, which collectively serves as mediators contact-dependent cell-cell communication to transmit extracellular cues into intracellular signals. As per their active counterparts, deregulation is strongly linked proliferative diseases. However, unlike receptors, whose catalytic activities thought initiate an signalling cascade, classified catalytically dead, raising question how non-catalytic functions...
Abstract EphB6 is an understudied ephrin receptor tyrosine pseudokinase that downregulated in multiple types of metastatic cancers. Unlike its kinase-active counterparts which autophosphorylate and transmit signals upon intercellular interaction, little known about how functions the absence intrinsic kinase activity. Here, we unveil a molecular mechanism cell-cell interaction driven by EphB6. We identify ephrinB1 as cognate ligand show trans with on neighboring cells leads to formation large...
Abstract The PEAK family of pseudokinases comprises PEAK1 and PEAK2 as well the recently-identified PEAK3. PEAK1/2 play fundamental roles in regulating tyrosine kinase signal output oncogenesis, while PEAK3 remains poorly-characterized. Here, we demonstrate that undergoes homotypic association heterotypic interaction with PEAK1/2. also recruits ASAP1/2, Cbl PYK2 adaptors Grb2 CrkII, binding dependent on dimerization. phosphorylation Y24 is dimerization Src activity, interestingly, decreased...
Abstract PEAK pseudokinases regulate cell migration, invasion and proliferation by recruiting key signaling proteins to the cytoskeleton. Despite lacking catalytic activity, alteration in their expression level is associated with several aggressive cancers. Here, we elucidate new molecular details of interactions adapter CrkII Grb2 scaffold protein 14-3-3. Our findings rationalize why dimerization has a crucial function signal transduction provide biophysical structural data unravel binding...
PEAK pseudokinases (PEAK1, PEAK2 and PEAK3) are important protein scaffolds that regulate cell migration, invasion proliferation by recruiting signalling effectors at the cytoskeleton [1,2].Despite lacking catalytic activity, alteration in expression level of family members is associated with several type aggressive cancers.An emerging thread function ability to utilise homo-and hetero-dimerisation dynamically integrate diversify cellular signals.Our lab was first structurally reveal a...
Abstract PEAK pseudokinases regulate cell migration, invasion and proliferation by recruiting key signaling proteins to the cytoskeleton. Despite lacking catalytic activity, alteration in their expression level is associated with several aggressive cancers. Here, we elucidate new molecular details of interactions adapter CrkII Grb2 scaffold protein 14-3-3. Our findings rationalize why dimerization has a crucial function signal transduction provide biophysical structural data unravel binding...
Abstract EphB6 is an understudied ephrin receptor tyrosine pseudokinase, the expression of which downregulated in multiple types metastatic cancers. Compared to its kinase-active counterparts, how regulates signal transduction absence intrinsic kinase activity remains unknown. Here, we unveil molecular details key mechanisms driven by EphB6. We identify ephrinB1 as a cognate ligand and demonstrate EphB6’s ability form extensive co-clusters at plasma membrane upon binding trans across...