- Protein Kinase Regulation and GTPase Signaling
- Enzyme Structure and Function
- Cellular transport and secretion
- Microtubule and mitosis dynamics
- Protein Structure and Dynamics
- Melanoma and MAPK Pathways
- Cancer-related Molecular Pathways
- Cell death mechanisms and regulation
- Cellular Mechanics and Interactions
- PI3K/AKT/mTOR signaling in cancer
- RNA and protein synthesis mechanisms
- Endoplasmic Reticulum Stress and Disease
- Hippo pathway signaling and YAP/TAZ
- Ion channel regulation and function
- Ubiquitin and proteasome pathways
- Cytokine Signaling Pathways and Interactions
- Virus-based gene therapy research
- Chemical Synthesis and Analysis
- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- Bacterial Genetics and Biotechnology
- Genetic factors in colorectal cancer
- Lipid Membrane Structure and Behavior
- RNA Research and Splicing
- 14-3-3 protein interactions
University of Cambridge
2015-2025
Institut Curie
2009
Inserm
2009
GlaxoSmithKline (United Kingdom)
2005
University of Hertfordshire
1998
University of Birmingham
1991-1996
Princeton University
1995
University of Liverpool
1990
University of Chicago
1985
p21-activated kinases (PAKs) serve as effector proteins for the GTP-binding Cdc42 and Rac. They are serine/threonine containing Cdc42/Rac interactive binding (CRIB) motif. The main aim of this study was to define minimal domain alphaPAK required binding. Eight stable PAK fragments varying lengths, each CRIB motif (residues 75-88), were expressed in Escherichia coli, their ability interact with Rac assessed using scintillation proximity assays, isothermal titration calorimetry, fluorescence...
The sequence of the imp operon plasmid TP110 (which belongs to Incl1 incompatibility group) has been determined, and is shown contain three open reading frames. This operon, involved in UV protection mutation, functionally analogous umuDC E.coli mucAB pKM101, which quite unrelated IncN group. umu muc operons however only two frames, coding for proteins approximately 16kD 46kD. high degree homology between (UmuD MucA) 46kD (UmuC MucB) clearly shows their relatedness. also extend gene...
IQGAP1 contains a domain related to the catalytic portion of GTPase-activating proteins (GAPs) for Ras small G proteins, yet it has no RasGAP activity and binds Rho family Cdc42 Rac1. It is thought that an effector Rac1 Cdc42, regulating cell-cell adhesion through E-cadherin-catenin complex, which controls formation maintenance adherens junctions. This study investigates binding interfaces Rac1-IQGAP1 Cdc42-IQGAP1 complexes. We mutated measured effects mutations on their affinity IQGAP1....
Transducer of Cdc42-dependent actin assembly protein 1 (TOCA1) is an effector the Rho family small G Cdc42. It contains a membrane-deforming F-BAR domain as well Src homology 3 (SH3) and protein-binding region (HR1) domain. TOCA1 binding to Cdc42 leads rearrangements, which are thought be involved in processes such endocytosis, filopodia formation, cell migration. We have solved structure HR1 TOCA1, providing first structural data for this protein. found that HR1, like closely related CIP4...
Cdc42 is a member of the Rho family small G proteins. Signal transduction events emanating from lead to cytoskeletal rearrangements, cell proliferation, and differentiation. Many effector proteins have been identified for Cdc42; however, it not clear how certain effectors specifically recognize bind Cdc42, as opposed Rac or Rho, in many cases, which controls what cellular events. Mutations were introduced into at residues: Met1, Val8, Phe28, Tyr32, Val33, Thr35, Val36, Phe37, Asp38, Tyr40,...
The small G proteins RalA/B have a crucial function in the regulatory network that couples extracellular signals with appropriate cellular responses. are an important component of Ras signaling pathway and, addition to their role membrane trafficking, implicated initiation and maintenance tumorigenic transformation human cells. RalA RalB share 85% sequence identity collaborate supporting cancer cell proliferation but markedly different effects. is mediating proliferation, while depletion...
Protein kinase C-related kinases (PRKs) are members of the protein C superfamily serine-threonine and can be activated by binding to Rho family GTPases via a Rho-binding motif known as an HR1 domain. Three tandem domains reside at N-terminus PRKs. We have assessed ability HR1a HR1b from three PRK isoforms (PRK1, PRK2, PRK3) interact with (RhoA, RhoB, RhoC). The affinities RhoA RhoC for construct encompassing both PRK1 were similar those domain alone, suggesting that these interactions...