Disease relevance of Tpr

• Pretreatment of both Tpr-Met-transformed NIH3T3 fibroblasts and of GTL-16 gastric carcinoma cells with K252a results in loss of their ability to form lung metastases in nude mice upon injection into the caudal vein [1].

High impact information on Tpr

• Small N-terminal htt fragments interact with the nuclear pore protein translocated promoter region (Tpr), which is involved in nuclear export [2].
• Identification of protein p270/Tpr as a constitutive component of the nuclear pore complex-attached intranuclear filaments [3].
• To establish which pathways might be differentially regulated, we have localized the constitutively activated Tpr-Met oncoprotein to the membrane using the c-src myristoylation signal [4].
• We demonstrate, by site-directed mutagenesis and coimmunoprecipitation experiments, that a leucine zipper motif within Tpr mediates dimerization of the tpr-met product and is essential for the transforming activity of the met oncogene [5].
• The mouse interferon-inducible gene Ifi204 product interacts with the Tpr protein, a component of the nuclear pore complex [6].

Biological context of Tpr

• A Met-hepatocyte growth factor receptor oncoprotein, Tpr-Met, generated by chromosomal rearrangement, fuses a protein dimerization motif with the cytoplasmic domain of the Met receptor, producing a cytosolic, constitutively activated tyrosine kinase [4].
• Thus, although the three Met oncogenes examined are similar in their dependency on a number of specific tyrosines for activity, the signaling strategy employed by Tpr-Met can be differentiated from that of the other two [7].
• Similarly, activating mutations introduced into a constitutively dimerized cytoplasmic form of Met (i.e. Tpr-Met) facilitate its autophosphorylation and oncogenic activity in the absence of Y8,9 phosphorylation [8].

Anatomical context of Tpr

• It comprises the intracellular moiety of Met linked to the dimerization domain of the nuclear envelope protein Tpr, thus functioning as a constitutively activated Met [9].

Associations of Tpr with chemical compounds

• Moreover, SU5416 caused reversion in NIH3T3 fibroblasts transformed by the oncogenic form of the receptor, Tpr-Met [10].

Analytical, diagnostic and therapeutic context of Tpr

• Accordingly, novel antibodies against the N- and C-terminus of Tpr identified the full-length protein as the major translation product in different somatic cell types; reinvestigation of Tpr localization by confocal microscopy corroborated a predominant localization at the nuclear pore complexes in these cells [11].
• Immunoprecipitation of Tpr from 32P-orthophosphate-labeled cells shows that it is a phosphoprotein [12].
• Anti-Tpr polyclonal monospecific antibodies (Ab) used for immunofluorescence staining labeled the nuclear envelope (NE) in a punctate pattern characteristic of nucleoporins and also yielded staining throughout the nuclear interior [6].

References