Mutant isoforms

Salt concentrations, especially inorganic anions (chloride), can vary widely without impacting the fluorescence of GFP and its mutant isoforms. 

As mentioned above BFPs are mutant isoforms of the Aequorea GFP carrying a histidine residue at position 66. In consequence, an imidazole is placed in the chromophore [52] causing a shift of the excitation and emission peaks towards shorter wavelengths. Further work led to the isolation of improved BFP isoforms with slightly higher molar extinction coefficient and quantum yield (increasing... 

Table 5. Naturally occurring CFPs and mutant isoforms...

For the GFP derived CFPs, amajCFP and its mutant isoforms as well as dstrCFP and clavCFP no data were found in published literature describing the pH-dependence, salt-sensitivity and temperature-stability of these proteins. As close relatives of GFP the mature GFP-derived CFPs are supposed to be able to tolerate relatively high temperature (up to 65 °C) before denaturing starts. However, this can only be speculated since experimental data are missing. 

The measurement of ER has become a standard assay in the clinical management of breast cancer. The presence of ERa identifies those breast cancer patients with a lower risk of relapse and better clinical outcome. Receptor status also provides a guideline for those tumors that may be responsive to hormonal intervention. But only about half of ER-positive patients respond to hormonal therapies. Of those who respond initially, most will eventually develop an estrogen unresponsive disease following a period of treatment even though ERa is often still present. Mutant receptors and constitutively active r eceptors as well as hormone-independent activation of the ERa are discussed. The involvement of ER 3 isoforms is under investigation. 

Buchler, M., et al. cDNA cloning of the hepatocyte canalicular isoform of the multidrug resistance protein, cMrp, reveals a novel conjugate export pump deficient in hyperbilirubinemic mutant rats. J. Biol. Chem. 1996, 271, 15091-15098. 

Myelin basic protein. In PNS myelin, MBP varies from approximately 5% to 18% of total protein, in contrast to the CNS, where it is close to 30% [ 1 ]. In rodents, the same four 21,18.5,17 and 14kDa MBPs found in the CNS are present in the PNS. In adult rodents, the 14kDa MBP is the most prominent component and is termed Pr in the PNS nomenclature. The 18.5 kDa component is present and is often referred to as the P, protein in the nomenclature of peripheral myelin proteins. Another species-specific variation in human PNS is that the major basic protein is not the 18.5 kDa isoform that is most prominent in the CNS but rather a form of about 17 kDa. It appears that MBP does not play as critical a role in myelin structure in the PNS as it does in the CNS. For example, the shiverer mutant mouse, which expresses no MBP (Table 4-2), has a greatly reduced amount of CNS myelin, with no compaction of the major dense line. By contrast, shiverer PNS has essentially normal myelin,both in amount and structure, despite the absence of MBP. This CNS/PNS difference in the role of MBP is probably because the cytoplasmic domain of P0 has an important role in stabilizing the major dense line of PNS myelin. Animals doubly deficient for P0 and MBP have a more severe defect in compaction of the PNS major dense line than P0-null mice, which indicates that both proteins contribute to compaction of the cytoplasmic surfaces in PNS myelin [23],... 

Rodents. Mice expressing wild-type and mutant human tau in nerve cells or glial cells have been found to develop numerous tau-immunoreactive cell bodies and processes. Abundant filaments made of hyperphosphorylated tau protein and neurodegeneration were present in some lines expressing single isoforms of mutant human tau protein [36, 37] (Fig. 45-8 and Fig. 45-9). Hyperphosphorylation of tau appeared to precede filament assembly and an... 

Some of the molecules responsible for hair-cell transduction have been identified. A few key molecules, some already described, have been identified as part of the transduction complex (Fig. 51-6). Myosin molecules clearly play essential roles, and hair cells express a variety of myosin isoforms. Because it is located at the tips of the stereocilia, near the tip-link anchors, myosin-1 c is the best candidate for the adaptation motor. Selective inhibition of a sensitized myosin- lc mutant with an ADP analog proved that this myosin participates in adaptation [14], although contribution by other myosins has yet to be ruled out. For example, mice with near-null mutations in myosin-7a have defects in auditory transduction that are consistent with alterations in the adaptation machinery, suggesting a central role for this myosin too [15]. 

An important stromal derived growth factor, SCF, appears to play a major role in mechanisms like this. SCF can be expressed as a membrane-bound molecule that can be subsequently cleaved to soluble protein. The physiological functions of these isoforms are not well known. The deficiencies in mature eythroid precursors and in pluripotent hematopoietic stem cells in SI mutant mice (McCulloch et al, 1965) indicated that the membrane-bound SCF isoform has an essential function in hematopoiesis. 

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