Characterization and cDNA cloning of phospholipase C-gamma, a major substrate for heparin-binding growth factor 1 (acidic fibroblast growth factor)-activated tyrosine kinase.
Heparin-binding growth factors (HBGFs) bind to high-affinity cell surface receptors which possess intrinsic tyrosine kinase activity. A Mr 150,000 protein phosphorylated on tyrosine in response to class 1 HBGF (HBGF-1) was purified and partially sequenced. On the basis of this sequence, cDNA clones were isolated from a human endothelial cell library and identified as encoding phospholipase C-gamma. Phosphorylation of phospholipase C-gamma in intact cells treated with HBGF-1 was directly demonstrated by using antiphospholipase C-gamma antibodies. Thus, HBGF-1 joins epidermal growth factor and platelet-derived growth factor, whose receptor activation leads to tyrosine phosphorylation and probable activation of phospholipase C-gamma.
Burgess
W H
WH
American Red Cross, Rockville, Maryland 20855.
Dionne
C A
CA
Kaplow
J
J
Mudd
R
R
Friesel
R
R
Zilberstein
A
A
Schlessinger
J
J
Jaye
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics* / Q000302:isolation & purification; D004789:Enzyme Activation; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D015723:Gene Library; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017468:Receptors, Fibroblast Growth Factor; D013379:Substrate Specificity; D010738:Type C Phospholipases / Q000235:genetics* / Q000378:metabolism
D007527:Isoenzymes; D015345:Oligonucleotide Probes; D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors; D004247:DNA; D011505:Protein-Tyrosine Kinases; D010738:Type C Phospholipases