Pten Phosphatase In The Regulation Of Lipid Signalling

Phosphoinositide-3 kinase (PI3K) is responsible for the phosphorylation and generation of PIP2 and PIP3. This phosphorylation is antagonised by a phosphatase that is encoded by the gene called PTEN MMAC1 TEP1 located on chromosome 10q23. The phosphatase, referred to here as PTEN, shows sequence homology to tensin (Steck et al. 1997). The phosphatase activity is essential for the normal functioning of PTEN (Tamura et al. 1999b). PTEN regulates the levels of the phosphoinositol phosphates by...

S100 Proteins in Remodelling of the Extracellular Matrix

ECM undergoes constant changes in terms of remodelling and renewal in a host of biological processes, such as morphogenesis, cell differentiation, wound healing, angiogenesis, cell motility, and also in the invasive and metastatic behaviour of cancers. A wide variety of proteinases are involved in the remodelling of the ECM. These enzymes and their inhibitors are known to be genetically regulated (see Sherbet and Lakshmi, 1997b). That ECM remodelling might involve S100A4 was demonstrated some...

Osteocalcin In Bone Metabolism And Osteotropism Of Cancer

Osteocalcin is a noncollagenous protein. It is the most abundant matrix protein of bone and dentine (Price, 1992). It is regarded as a marker of bone turnover and metabolism, where bone resorption and formation are coupled. Osteocalcin is syn-thesised exclusively by osteoblasts and secreted into the extracellular matrix (ECM) during bone mineralisation. It is released also during osteoclastic degradation. Therefore, it is considered to be a marker of bone formation when formation and resorption...

S100A4 Expression and Metastatic Potential of Cancers

The considerable influence that S100A4 exerts over cell adhesion, motility, and cell proliferation has prompted the investigation of the possible relevance of its expression in tumour development and their progression to the metastatic state. S100A4 is found in a variety of normal tissues of both murine and human origin (Grigorian et al. 1994 Gibbs et al. 1995). It occurs in normal adult rat tissues such as smooth muscle, brown adipose tissue, and the liver. Other tissues, e.g., normal breast...

The Fimbrin Family Of Actinbinding Proteins

Fimbrins are EF-hand calcium-binding proteins that actively participate in binding to and bundling of actin. In actin filaments, one molecule of fimbrin might bind eight actin monomers under optimal conditions Namba et al. 1992 . Fimbrins are highly conserved in evolution, with regard to both their structure and function. Fimbrin from diverse origins, e.g., from Dictyostelium discoideum to humans, share structural and biochemical properties. Fimbrin-like proteins have also been isolated from...

Camkiv

FIGURE 8 Phosphorylation of the transcription factors CREB cyclic AMP response element binding protein and ATF in the negative and positive regulation of genetic activity. The Ca2 CaM-activated protein kinases CAMKIV and CAMKII phosphorylate specific positive and negative regulatory serine residues of the transcription factors, which therefore differentially transactivate the responsive genes. targeted and conveyed to specific subcellular compartments for eliciting cellular responses. This...

The Gelsolin Family Of Calciumbinding Proteins

Actin-binding proteins constitute a large family of proteins that actively participate in actin bundling, nucleation, actin capping, and severing. Gelsolin, severin, and villin are three important proteins of the gelsolin family of actin-binding proteins that will be discussed here, for they possess the remarkable property of rapidly reorganising the cytoskeleton and also rapidly modulating, in a Ca2 -dependent manner, cell shape, substrate adhesion, and cell locomotion. Gelsolin in Severing...

Osteotropism Of Metastatic Dissemination

Metastatic spread of cancer is a nonrandom process. The perceived organ specificity of metastasis can be attributed to a variety of factors intrinsic to the cancer cell as well as to the target organs see Sherbet, 1982 for review . Metastatic spread to the bone is a common occurrence in certain forms of cancer. It has been argued often that bone metastases can activate the processes of bone metabolism. For that reason osteocalcin has been regarded as a potential surrogate method for detecting...

Calpains In Cancer Growth And Progression

Calpain is significantly involved, as discussed above, in a number of physiological processes that are integral features of the development and progression of cancer. We have seen that the suppressor phosphoprotein p53, which is closely linked with the control of cell cycle progression, is degraded by calpain. Mutations of p53 gene are a common event in tumorigenesis, and these lead to the abrogation of normal checkpoint control function exerted by wild-type p53. We have noted also that calpain...

Calcineurin In Cell Proliferation And Adhesionrelated Phenomena

Calcineurin has been implicated in a number of physiological events, such as cell proliferation, cell death, and signal transduction, and in immunosuppression. It also has been implicated in certain functions of the nervous system, e.g., in neurotransmission. The discussion here will be restricted mainly to areas pertinent to the biological behaviour of cancers, although some reference will be made to Alzheimer's disease, in which cytoskeletal abnormalities occur prominently. The regulation of...

The Role Of Thymosin Family Actinbinding Proteins In Actin Dynamics

The beta thymosins constitute an important family of actin-binding proteins, which are recognised as major participants in the regulation of actin dynamics. Among its members are TP4, TP 10, and TP 15, which are the most intensively investigated forms of thymosin. TP4 is a 4.5-kDa protein consisting of 43 amino acid residues. TP 14 is another protein isolated from the sea urchin, that has 40 amino acid residues and a molecular size of 4.53 kDa and bears a high degree of sequence homology to TP4...

Recoverin and Cancer Associated Retinopathy in Small Cell Lung Cancer

A degeneration of the retina is infrequently associated as a paraneoplastic condition with some forms of cancer. This condition, often described as cancer-associated retinopathy CAR , is an autoimmune syndrome involving the degeneration of the photoreceptor cells of the eyes. Injection of RCN had previously been shown to induce degeneration of photoreceptor cells of the eyes of Lewis rats, and this was correlated with high titres of RCN antibodies in the circulation Adamus et al. 1994 . There...

Calreticulin in Neoplasia

Although the above discussion indicates a significant involvement of calreticulin in cell adhesion and possibly also in cell proliferation, only a few studies have dealt with its occurrence in tumours. Of the multiple functions attributed to calreticulin, its perceived effects on cell proliferation are the most relevant in relation to cancer. Calreticulin is one of several peptides of human breast cancers studied by Franzen et al. 1997 . They state that it is expressed at higher levels in...

Annexins

Several non-EF-hand CBPs have been identified and sequenced. Of these, annexins have been studied extensively. Annexins form a family of structurally related and highly conserved proteins that bind phospholipids in a Ca2 -dependent manner. Several annexins have been identified and some of these have been well characterised, e.g., annexins I, IV, V, and XII. A 40-kDa annexin, distinct from annexin XII, has been reported from Hydra vulgaris Schlaepfer et al. 1992a . Although basically annexins...