Robert Gourlay
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View article: Phosphorylation enables progressive microtubule-associated protein proteolysis and functionalisation during neural development
Phosphorylation enables progressive microtubule-associated protein proteolysis and functionalisation during neural development Open
Neurological diseases are frequently characterised by dysregulation of the microtubule cytoskeleton, which is critical for neuronal integrity and functioning. However, the precise mechanisms by which microtubule dynamics are regulated duri…
View article: NEK7 phosphorylation of cortactin modulates the migratory capacity of cells expressing EML4-ALK V3
NEK7 phosphorylation of cortactin modulates the migratory capacity of cells expressing EML4-ALK V3 Open
EML4-ALK is a common oncogenic driver of non-small cell lung cancer. Distinct EML4-ALK variants cause different rates of disease progression, with patients expressing variant 3 (V3) exhibiting accelerated metastasis. Cells expressing EML4-…
View article: Regulation of Human PINK1 ubiquitin kinase by Serine167, Serine228 and Cysteine412 phosphorylation
Regulation of Human PINK1 ubiquitin kinase by Serine167, Serine228 and Cysteine412 phosphorylation Open
Loss-of-function mutations in the human PINK1 kinase (hPINK1) are causative of early-onset Parkinson’s disease (PD). Activation of hPINK1 induces phosphorylated ubiquitin to initiate removal of damaged mitochondria by autophagy. Previously…
View article: Regulation of Human PINK1 ubiquitin kinase by Serine167, Serine228 and Cysteine412 phosphorylation
Regulation of Human PINK1 ubiquitin kinase by Serine167, Serine228 and Cysteine412 phosphorylation Open
Loss-of-function mutations in the human PINK1 kinase ( h PINK1) are causative of early-onset Parkinson’s disease (PD). Activation of h PINK1 induces phosphorylated ubiquitin to initiate removal of damaged mitochondria by autophagy. Previou…
View article: An affinity-directed phosphatase, AdPhosphatase, system for targeted protein dephosphorylation
An affinity-directed phosphatase, AdPhosphatase, system for targeted protein dephosphorylation Open
Reversible protein phosphorylation, catalyzed by protein kinases and phosphatases, is a fundamental process that controls protein function and intracellular signaling. Failure of phospho-control accounts for many human diseases. While a ki…
View article: Co-ordinated control of the ADP-heptose/ALPK1 signalling network by the E3 ligases TRAF6, TRAF2/c-IAP1 and LUBAC
Co-ordinated control of the ADP-heptose/ALPK1 signalling network by the E3 ligases TRAF6, TRAF2/c-IAP1 and LUBAC Open
ADP-heptose activates the protein kinase ALPK1 triggering TIFA phosphorylation at Thr9, the recruitment of TRAF6 and the subsequent production of inflammatory mediators. Here, we demonstrate that ADP-heptose also stimulates the formation o…
View article: PKC isoforms activate LRRK1 kinase by phosphorylating conserved residues (Ser1064, Ser1074 and Thr1075) within the CORB GTPase domain
PKC isoforms activate LRRK1 kinase by phosphorylating conserved residues (Ser1064, Ser1074 and Thr1075) within the CORB GTPase domain Open
Leucine-rich-repeat-kinase 1 (LRRK1) and its homolog LRRK2 are multidomain kinases possessing a ROC-CORA-CORB containing GTPase domain and phosphorylate distinct Rab proteins. LRRK1 loss of function mutations cause the bone disorder osteos…
View article: PKC isoforms activate LRRK1 kinase by phosphorylating conserved residues (Ser1064, Ser1074 and Thr1075) within the CORB GTPase domain
PKC isoforms activate LRRK1 kinase by phosphorylating conserved residues (Ser1064, Ser1074 and Thr1075) within the CORB GTPase domain Open
Abstract Leucine-rich-repeat-kinase 1 (LRRK1) and its homologue LRRK2 are multidomain kinases possessing a ROC-CORA-CORB containing GTPase domain and phosphorylate distinct Rab proteins. LRRK1 loss of function mutations cause the bone diso…
View article: Coordinated control of the ADP-heptose/ALPK1 signalling network by the E3 ligases TRAF6, TRAF2/c-IAP1 and LUBAC
Coordinated control of the ADP-heptose/ALPK1 signalling network by the E3 ligases TRAF6, TRAF2/c-IAP1 and LUBAC Open
Summary ADP-heptose activates the protein kinase ALPK1 triggering TIFA phosphorylation at Thr9, the recruitment of TRAF6 and the subsequent production of inflammatory mediators. Here, we demonstrate that ADP-heptose also stimulates the for…
View article: PKC isoforms activate LRRK1 kinase by phosphorylating conserved residues (Ser1064, Ser1074 and Thr1075) within the COR<sub>B</sub>GTPase domain
PKC isoforms activate LRRK1 kinase by phosphorylating conserved residues (Ser1064, Ser1074 and Thr1075) within the COR<sub>B</sub>GTPase domain Open
Leucine-rich-repeat-kinase 1 (LRRK1) and its homologue LRRK2 are multidomain kinases possessing a ROC-COR A -COR B containing GTPase domain and phosphorylate distinct Rab proteins. LRRK1 loss of function mutations cause the bone disorder o…
View article: PKC isoforms activate LRRK1 kinase by phosphorylating conserved residues (Ser1064, Ser1074 and Thr1075) within the CORB GTPase domain
PKC isoforms activate LRRK1 kinase by phosphorylating conserved residues (Ser1064, Ser1074 and Thr1075) within the CORB GTPase domain Open
Abstract Leucine-rich-repeat-kinase 1 (LRRK1) and its homologue LRRK2 are multidomain kinases possessing a ROC-CORA-CORB containing GTPase domain and phosphorylate distinct Rab proteins. LRRK1 loss of function mutations cause the bone diso…
View article: An ERK5-KLF2 signalling module regulates early embryonic gene expression dynamics and stem cell rejuvenation
An ERK5-KLF2 signalling module regulates early embryonic gene expression dynamics and stem cell rejuvenation Open
Summary The ERK5 MAP kinase signalling pathway drives transcription of naïve pluripotency genes in mouse Embryonic Stem Cells (mESCs). However, how ERK5 impacts on other aspects of mESC biology has not been investigated. Here, we employ qu…
View article: Deciphering the LRRK code: LRRK1 and LRRK2 phosphorylate distinct Rab proteins and are regulated by diverse mechanisms
Deciphering the LRRK code: LRRK1 and LRRK2 phosphorylate distinct Rab proteins and are regulated by diverse mechanisms Open
Autosomal dominant mutations in LRRK2 that enhance kinase activity cause Parkinson's disease. LRRK2 phosphorylates a subset of Rab GTPases including Rab8A and Rab10 within its effector binding motif. Here, we explore whether LRRK1, a less …
View article: Deciphering the LRRK code: LRRK1 and LRRK2 phosphorylate distinct Rab proteins and are regulated by diverse mechanisms
Deciphering the LRRK code: LRRK1 and LRRK2 phosphorylate distinct Rab proteins and are regulated by diverse mechanisms Open
Much attention has focused on LRRK2, as autosomal dominant missense mutations that enhance its kinase activity cause inherited Parkinson’s disease. LRRK2 regulates biology by phosphorylating a subset of Rab GTPases including Rab8A and Rab1…
View article: Functional Diversification of SRSF Protein Kinase to Control Ubiquitin-Dependent Neurodevelopmental Signaling
Functional Diversification of SRSF Protein Kinase to Control Ubiquitin-Dependent Neurodevelopmental Signaling Open
Conserved protein kinases with core cellular functions have been frequently redeployed during metazoan evolution to regulate specialized developmental processes. The Ser/Arg (SR)-rich splicing factor (SRSF) protein kinase (SRPK), which is …
View article: Characterisation of the biochemical and cellular roles of native and pathogenic amelogenesis imperfecta mutants of FAM83H
Characterisation of the biochemical and cellular roles of native and pathogenic amelogenesis imperfecta mutants of FAM83H Open
The majority of mutations identified in patients with amelogenesis imperfecta have been mapped to FAM83H. As FAM83H expression is not limited to the enamel, how FAM83H contributes to amelogenesis is still largely unknown. We previously rep…
View article: Functional diversification of Ser-Arg rich protein kinases to control ubiquitin-dependent neurodevelopmental signalling
Functional diversification of Ser-Arg rich protein kinases to control ubiquitin-dependent neurodevelopmental signalling Open
SUMMARY Conserved protein kinases with core cellular functions have been frequently redeployed during metazoan evolution to regulate specialized developmental processes. Ser-Arg Repeat Protein Kinase (SRPK) is one such conserved eukaryotic…
View article: Pathogenic FAM83G palmoplantar keratoderma mutations inhibit the PAWS1:CK1α association and attenuate Wnt signalling.
Pathogenic FAM83G palmoplantar keratoderma mutations inhibit the PAWS1:CK1α association and attenuate Wnt signalling. Open
Background: Two recessive mutations in the FAM83G gene, causing A34E and R52P amino acid substitutions in the DUF1669 domain of the PAWS1 protein, are associated with palmoplantar keratoderma (PPK) in humans and dogs respectively. We have …
View article: Phosphoproteomics reveals that the hVPS34 regulated SGK3 kinase specifically phosphorylates endosomal proteins including Syntaxin-7, Syntaxin-12, RFIP4 and WDR44
Phosphoproteomics reveals that the hVPS34 regulated SGK3 kinase specifically phosphorylates endosomal proteins including Syntaxin-7, Syntaxin-12, RFIP4 and WDR44 Open
The serum- and glucocorticoid-regulated kinase (SGK) isoforms contribute resistance to cancer therapies targeting the PI3K pathway. SGKs are homologous to Akt and these kinases display overlapping specificity and phosphorylate several subs…
View article: Pathogenic FAM83G palmoplantar keratoderma mutations inhibit the PAWS1:CK1α association and attenuate Wnt signalling.
Pathogenic FAM83G palmoplantar keratoderma mutations inhibit the PAWS1:CK1α association and attenuate Wnt signalling. Open
Background: Two recessive mutations in the FAM83G gene, causing A34E and R52P amino acid substitutions in the DUF1669 domain of the PAWS1 protein, are associated with palmoplantar keratoderma (PPK) in humans and dogs respectively. We have …
View article: Phosphoproteomics reveals that the hVPS34 regulated SGK3 kinase specifically phosphorylates endosomal proteins including Syntaxin-7, Syntaxin-12, RFIP4 and WDR44
Phosphoproteomics reveals that the hVPS34 regulated SGK3 kinase specifically phosphorylates endosomal proteins including Syntaxin-7, Syntaxin-12, RFIP4 and WDR44 Open
The serum- and glucocorticoid-regulated kinase (SGK) isoforms contribute resistance to cancer therapies targeting the PI3K pathway. SGKs are homologous to Akt and these kinases display overlapping specificity and phosphorylate several subs…
View article: FAM83D directs protein kinase CK1α to the mitotic spindle for proper spindle positioning
FAM83D directs protein kinase CK1α to the mitotic spindle for proper spindle positioning Open
Summary The concerted action of many protein kinases helps orchestrate the error-free progression through mitosis of mammalian cells. The roles and regulation of some prominent mitotic kinases, such as cyclin-dependent kinases, are well-es…
View article: Human Family With Sequence Similarity 83 Member B (Fam83B); A Target Enabling Package
Human Family With Sequence Similarity 83 Member B (Fam83B); A Target Enabling Package Open
FAM83A-H are newly identified oncogenes characterised by a conserved DUF1669 domain. FAM83B can substitute for RAS to promote malignant transformation. Ablation of FAM83B or mutation of Lys230 inhibits malignant phenotypes, implicating FAM…
View article: Human Family With Sequence Similarity 83 Member B (Fam83B); A Target Enabling Package
Human Family With Sequence Similarity 83 Member B (Fam83B); A Target Enabling Package Open
FAM83A-H are newly identified oncogenes characterised by a conserved DUF1669 domain. FAM83B can substitute for RAS to promote malignant transformation. Ablation of FAM83B or mutation of Lys230 inhibits malignant phenotypes, implicating FAM…
View article: Human Family With Sequence Similarity 83 Member B (Fam83B); A Target Enabling Package
Human Family With Sequence Similarity 83 Member B (Fam83B); A Target Enabling Package Open
FAM83A-H are newly identified oncogenes characterised by a conserved DUF1669 domain. FAM83B can substitute for RAS to promote malignant transformation. Ablation of FAM83B or mutation of Lys230 inhibits malignant phenotypes, implicating FAM…