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What is Wnt Signalling? The Wnt signalling pathway is an evolutionarily conserved pathway that plays critical roles in the regulation of determining cell fate, polarity, migration, neural patterning and organogenesis during embryonic development. Components of this signalling pathway were discovered in the 1980’s by a number of researchers working in both mouse and Drosophila models. An overview of Wnt Signalling The name ‘Wnt’ originated from a combination of the Drosophila segment polarity gene wingless (wg) (Sharma, 1973) and the vertebrate homolog, integrated-1 (int-1) (Nusse et al.,1990).Wg was shown …

Cell Signalling Cell signalling pathways have an important role in integrating a plethora of extracellular and intracellular signals to produce a controlled optimal output of signals, and results in the regulation of specific cellular responses. This is crucial for the homeostasis of the cell, and the deregulation of signalling pathways has been related to a number of diseases including cancer (Choudhary and Mann 2010).  Receptor signalling Cells integrate signals from the extracellular matrix by expressing specific receptors on the plasma membrane that can be activated by a specific ligand. Receptors then transduce the ex …

Bone Morphogenetic Proteins (BMP) were first discovered in the 1960s by Dr.Marshall Urist, an orthopaedic surgeon at UCLA (Urist 1965). BMPs are classically associated with their roles in limb development, induction of cartilage and bone growth. However, it has been since clarified that Bone Morphogenetic proteins (BMPs) are involved in many more diverse biological processes, such as stem cell and organ formation, muscle development, iron metabolism, vascular biology and cancer (D. P. Brazil et al.2015). The BMPs belong to the TGF-β superfamily and are glycosylated, extracellular matrix-associated molecules. The constituents of the BMP signalling pathway have also been implicated in d …

Protein kinase B or AKT (PKB) is a serine/threonine kinase. In mammals it is comprised of 3 highly homologous isoforms PKBα (Akt1), PKBβ (Akt2), and PKBγ (Akt3) (Manning and Cantley 2007). AKT signalling is activated in response to a variety of hormones, growth factors and extracellular matrix (ECM) components. The serine/threonine kinase AKT is involved in the regulation of a number of cellular processes including cell growth, proliferation, metabolism and cell survival. AKT Signalling Activation AKTs are activated by receptor tyrosine kinases (RTKs). RTKs activate phosphatidylinositol 3-kinase (PI3K) through tyrosine phosphorylation of adaptor proteins …

LATS kinases belong to a family of proteins that, in mammals, are comprised of two isoforms, LATS1 and LATS2. Originally identified in Drosophila melanogaster as Warts kinase, LATS1 and LATS2 serine/threonine kinases have been shown to be tumour suppressors (Edwards and Munger 2004). The original homologue of LATS was described as the dlats/warts tumour suppressor in two independent screens in Drosophila (Justice et al. 1995, Xu et al. 1995). Dlats and warts encoded the same gene so in this thesis the original homologue of LATS is warts (wts). Homozygous loss of the warts gene in Drosophila formed greatly overgrown somatic cells which lead to the hypothesis that warts is a tumour suppr …

MST2/Hippo PathwayMammalian Sterile Twenty (MST) pathways have been identified as a homologue of the ste20 kinase from Saccharomyces cerevisiae (Creasy and Chernoff 1995). The MST2/Hippo pathway has been identified as a master regulator of cell proliferation, cell death and cell differentiation (Yu and Guan 2013).The Hippo Pathway in drosophilaIn Drosophila, the Hippo pathway was first discovered with the identification of Fat and expanded proteins which were shown to regulate cell proliferation (Boedigheimer and Laughon 1993, Mahoney et al. 1991). The Hippo pathway in Drosophila is composed of a number of core proteins which have homologues in mammalian cells. The Hippo pathway was ma …

A wide variety of cell surface receptors activate Ras GTPase, including the tyrosine receptor linked to the epidermal growth factor receptor (EGFR) (Wells 1999). Upon receptor stimulation, son of sevenless (SOS) stimulates Ras to change from GDP to GTP resulting in Ras activation (Geyer and Wittinghofer 1997).Ras GTPaseRas GTPase shuttles between inactive GDP-bound and active GTP-bound conformation (Colicelli 2004). The best characterised isoforms of Ras GTPase are K-Ras, H-Ras and N-Ras, which are demonstrated to be mutated in 30% of human tumours (Repasky et al. 2004). Activated Ras phosphorylates and activates the Ser/Thr kinase Raf. The three isoforms of Raf are B-Raf, Raf-1 and A- …

IntroductionThe human kinome is estimated to contain 518 genes, in comparison to the estimated 180 genes that comprise the phosphatome (Arena et al., 2005). These kinase genes represent a significant fraction of all eukaryotic genes, highlighting the prominent role of these enzymes in controlling key cellular functions (Manning et al., 2002). The first oncogene to be identified and characterised, Src, was found to be a tyrosine kinase (Collett et al., 1980; Czernilofsky et al., 1980). The isolation of this tyrosine kinase in 1980 came 7 years before the first tyrosine phosphatase, PTP1B, which was identified in 1987 and purified in 1988 (Lim Tung et al., 1987; Tonks et al., 1988). Inve …

IQGAP1: IQ-motif containing GTPase-activating-like protein-1 reviewIQ motif-containing GTPase-activating-like protein-1 (IQGAP1) is a 190 KDa protein that belongs to a conserved family of scaffolds and was first identified in 1994 (Weissbach et al. 1994). The IQGAP family are comprised of three isoforms IQGAP1, IQGAP2 and IQGAP3 in mammals.IQGAP expressionIQGAP homologs are found in a variety of organisms and the mammalian IQGAPs share 20% amino acid identity with Iqg1p in Saccharomyces cerevisiae (Abel et al. 2015). In humans, IQGAP1 is expressed ubiquitously in tissues while IQGAP2 is expressed mainly in the liver and IQGAP3 is identified in the brain, lung, testis and colon (Whi …