The alternatively spliced exon of the platelet-derived growth factor A chain encodes a nuclear targeting signal

1989 ◽  
Vol 9 (5) ◽  
pp. 2251-2253
Author(s):  
D W Maher ◽  
B A Lee ◽  
D J Donoghue
Keyword(s):  
Growth Factor ◽  
Dihydrofolate Reductase ◽  
Platelet Derived Growth Factor ◽  
Nuclear Targeting ◽  
Factor B ◽  
Cytoplasmic Proteins ◽  
C Terminus ◽  
Alternatively Spliced ◽  
Targeting Signal ◽  
A Chain

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.

scholarly journals The alternatively spliced exon of the platelet-derived growth factor A chain encodes a nuclear targeting signal.

1989 ◽  
Vol 9 (5) ◽  
pp. 2251-2253 ◽  
Author(s):  
D W Maher ◽  
B A Lee ◽  
D J Donoghue
Keyword(s):  
Growth Factor ◽  
Dihydrofolate Reductase ◽  
Platelet Derived Growth Factor ◽  
Nuclear Targeting ◽  
Factor B ◽  
Cytoplasmic Proteins ◽  
C Terminus ◽  
Alternatively Spliced ◽  
Targeting Signal ◽  
A Chain

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.

scholarly journals Alternatively spliced platelet-derived growth factor A-chain transcripts are not tumor specific but encode normal cellular proteins.

1990 ◽  
Vol 10 (11) ◽  
pp. 6051-6054 ◽  
Author(s):  
R M Young ◽  
A E Mendoza ◽  
T Collins ◽  
S H Orkin
Keyword(s):  
Growth Factor ◽  
Immunohistochemical Localization ◽  
Platelet Derived Growth Factor ◽  
Chain Gene ◽  
S1 Nuclease ◽  
Normal Tissues ◽  
Alternative Mrna Splicing ◽  
Alternatively Spliced ◽  
A Chain ◽  
Nuclease Mapping

Two platelet-derived growth factor A-chain proteins, termed short and long A chains, are generated as a result of alternative mRNA splicing of exon 6 of the A-chain gene. S1 nuclease mapping and polymerase chain reaction analyses demonstrate that both short and long A-chain transcripts are expressed in a variety of normal tissues. In addition, immunohistochemical localization of long A-chain protein reveals a cellular distribution identical to that observed with platelet-derived growth factor heteroserum.

Alternatively spliced platelet-derived growth factor A-chain transcripts are not tumor specific but encode normal cellular proteins

1990 ◽  
Vol 10 (11) ◽  
pp. 6051-6054
Author(s):  
R M Young ◽  
A E Mendoza ◽  
T Collins ◽  
S H Orkin
Keyword(s):  
Growth Factor ◽  
Immunohistochemical Localization ◽  
Platelet Derived Growth Factor ◽  
Chain Gene ◽  
S1 Nuclease ◽  
Normal Tissues ◽  
Alternative Mrna Splicing ◽  
Alternatively Spliced ◽  
A Chain ◽  
Nuclease Mapping

Two platelet-derived growth factor A-chain proteins, termed short and long A chains, are generated as a result of alternative mRNA splicing of exon 6 of the A-chain gene. S1 nuclease mapping and polymerase chain reaction analyses demonstrate that both short and long A-chain transcripts are expressed in a variety of normal tissues. In addition, immunohistochemical localization of long A-chain protein reveals a cellular distribution identical to that observed with platelet-derived growth factor heteroserum.

scholarly journals Identification of a cell retention signal in the B-chain of platelet-derived growth factor and in the long splice version of the A-chain.

1991 ◽  
Vol 2 (7) ◽  
pp. 503-512 ◽  
Author(s):  
A Ostman ◽  
M Andersson ◽  
C Betsholtz ◽  
B Westermark ◽  
C H Heldin
Keyword(s):  
Amino Acid ◽  
Growth Factor ◽  
Splice Variant ◽  
Platelet Derived Growth Factor ◽  
Conserved Sequence ◽  
Alternatively Spliced ◽  
A Cell ◽  
Producer Cell ◽  
A Chain ◽  
Carboxy Terminal

The B-chain homodimer of platelet-derived growth factor (PDGF) is only very inefficiently secreted and remains largely associated with the producer cell; in contrast, the dimer of the short, and most common, splice variant of the A-chain is secreted. To identify the structural background to the differences in the secretory pattern between the different isoforms of PDGF, a set of chimeric PDGF A/B cDNAs was generated and expressed in COS cells. Analyses of the biosynthesis and processing of the corresponding products led to the identification of a determinant for cell association in the carboxy-terminal third of the PDGF B-chain precursor. Introduction of stop codons at various positions in the carboxy-terminal prosequence of the PDGF B-chain localized this determinant to an 11-amino-acid-long region (amino acids 219-229). This region contains an 8-amino-acid-long basic sequence that is homologous to a sequence present in an alternatively spliced longer version of the PDGF A-chain. In contrast to the short splice variant, the long splice A-chain version, like the B-chain, was found to remain predominantly cell associated. Thus, we have identified a conserved sequence that inhibits the secretion of some of the PDGF isoforms. Our data also suggest that switching of splicing patterns can be a mechanism to regulate the formation of secreted or cell-associated forms of PDGF-AA and possibly other growth factors.

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