Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.5.1.3 (dihydrofolate reductase)
 5,819 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously shown that the SIS/platelet-derived growth factor B chain contains a nuclear targeting signal near its C terminus. Here we show that the platelet-derived growth factor A chain also contains a nuclear targeting signal encoded by an exon which is subject to alternative splicing. This sequence is capable of targeting a nonsecreted form of the A chain to the nucleus and can also target the cytoplasmic proteins dihydrofolate reductase, chloramphenicol acetyltransferase, and pyruvate kinase to the nucleus.
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PMID:The alternatively spliced exon of the platelet-derived growth factor A chain encodes a nuclear targeting signal. 274 50

Two cDNA clones encoding distinct forms of plastid pyruvate kinase (designated Pka and Pkg) have recently been characterized. Pkg is found in both leucoplasts and chloroplasts, whereas Pka is present only in leucoplasts. The precursors of these proteins have different in vitro import characteristics. The Pkg precursor behaves like a typical stromal protein precusor with both types of plastid. In contrast, Pka precursors accumulate on the outer envelope membrane of leucoplasts under the same assay conditions and require a higher level of ATP for import into the organelle. Interestingly, the binding of Pka precursors to chloroplasts cannot be detected at any tested level of ATP even though the precursors are imported into the organelle at higher concentrations of ATP. Various N-terminal deletions and chimeric fusions were used to examine the translocation signaling mechanism of the Pka precursor. The N-terminal 83-amino-acid segment of Pka contains a transit peptide that is capable of directing dihydrofolate reductase and the mature body of Pkg into both types of plastid. Unlike the complete Pka precursor, these fusion proteins behave like typical stromal protein precursors. The behavior of the Pka transit peptide is influenced by a 19-amino-acid domain (-P-S-S-I-E-V-D-A-V-T-E-T-E-L-K-E-N-G-F-) located immediately downstream of the N-terminal 83-residue segment. Deletion of this domain from Pka alters its import properties such that it resembles a typical stromal protein precursor. Re-introduction of the 19-residue domain into the Dhfr fusion protein alters its import characteristics to resemble that of the complete Pka precursor. This 19-amino-acid domain can also influence the function of transit sequences from other precursors when it is placed immediately behind the transit peptide. These results suggest that this 19-amino-acid domain plays an important role in governing the import characteristics of the Pka precursor. We have named this 19-residue segment the "import modifying domain."
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PMID:Import characteristics of a leucoplast pyruvate kinase are influenced by a 19-amino-acid domain within the protein. 762 84