Oncogene product

The relationship between the two receptors for NGF is complex and not yet completely understood. It has been suggested that the functional form of the NGF receptor is a heterodimer of p75 and pl40 proteins. BDNF and NT-3 bind to p75, but the functional receptors for these neurotrophins are the proto-oncogene products of and trkQ. 

The leucine zipper motif (see Chapter 3) was first recognized in the amino acid sequences of a yeast transcription factor GCN4, the mammalian transcription factor C/EBP, and three oncogene products, Fos, Jun and Myc, which also act as transcription factors. When the sequences of these proteins are plotted on a helical wheel, a remarkable pattern of leucine residues... 

Pai, E.F., et al. Structure of the guanine-nucleotide-binding domain of the Ha-ras oncogene product p21 in the triphosphate conformation. Nature 341 209-214,... 

Morrison, D. K., Kaplan, D. R., Rapp, U., and Roberts, T. M. (1988). Signal transduction from membrane to cytoplasm growth factors and membrane-bound oncogene products increase Raf-1 phosphorylation and associated protein kinase activity. Proc. Natl. Acad. Sci. USA 85 8855-8859. 

Sagata, N., Oskarsson, M., Copeland, T Brumbaugh, J and Vande Woude, G. F. (1988). Function of c-mos proto-oncogene product in meiotic maturation in Xenopus oocytes. Nature 335 519-525. 

Paules, R. S., Buccione, R., Moschel, R. C., Vande Woude, G. F., and Eppig, J. J. (1989). Mouse mos proto-oncogene product is present and functions during oogenesis. Proc. Natl. Acad. Sci. USA 86 5395-5399. 

For example, c-Fos is heavily phosphorylated on a series of serine residues in the C-terminal domain of the protein by several types of protein kinases. The likely functional importance of these phosphorylation sites is indicated by the fact that the difference between c-Fos (the normal cellular form of the protein) and v-Fos (the viral oncogene product) is a frameshift mutation in the v-Fos protein, which obliterates the phosphorylated serine residues. It is speculated that the loss of these phosphorylation sites removes one mechanism by which the cell can regulate the protein, thereby leading to cellular transformation. 

Since then, a plethora of tyrosine-phosphorylated proteins has been discovered. Originally, tyrosine phosphorylation was believed to be involved primarily in regulating cell proliferation, since many oncogene products and growth factor receptors are protein tyrosine kinases (PTKs). However, it has become clear that tyrosine phosphorylation is involved in regulating a variety of cellular processes. In fact, the nervous system contains a large variety of PTKs and protein tyrosine phosphatases (PTPs), and some of these are exclusively expressed in neuronal tissues. Figure 24-1 shows the... 

Andoniou, C. E., et al.. The Cbl proto-oncogene product negatively regulates the Src-family tyrosine kinase Eyn by enhancing its degradation. Mol Cell Biol, 2000, 20(3), 851-67. 

Momand, j., et ah. The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell, 1992, 69(7), 1237-45. 

The effects of insulin on transcription are shown on the left of the illustration. Adaptor proteins Crb-2 and SOS ( son of sevenless ) bind to the phosphorylated IRS (insulin-receptor substrate) and activate the G protein Ras (named after its gene, the oncogene ras see p.398). Ras activates the protein kinase Raf (another oncogene product). Raf sets in motion a phosphorylation cascade that leads via the kinases MEK and ERK (also known as MARK, mitogen-activated protein kinase ) to the phosphorylation of transcription factors in the nucleus. 

Cysteine farnesylation of the ras oncogene product Ras is required for its transforming... 

Meisner, H., and M. P. Czech. Coupling of the proto-oncogene product c-Cbl to the epidermal growth factor receptor. J Biol Chem. 270 25332-25335.1995. 

If strong promoters such as T7 are used and the level of functional GroESL does not increase proportionally, correct folding may not occur. One effective way to increase solubility of foreign proteins in E. coli is by coproduction of the bacterial chaperones GroESL (Yasukawa et al., 1995). Coproduction of GroESL with transcription factors and oncogene products resulted in soluble protein. A... 

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