Binding of SH2 domains of phospholipase C gamma 1, GAP, and Src to activated growth factor receptors.
Phospholipase C gamma 1 (PLC gamma 1) and p21ras guanosine triphosphatase (GTPase) activating protein (GAP) bind to and are phosphorylated by activated growth factor receptors. Both PLC gamma 1 and GAP contain two adjacent copies of the noncatalytic Src homology 2 (SH2) domain. The SH2 domains of PLC gamma 1 synthesized individually in bacteria formed high affinity complexes with the epidermal growth factor (EGF)- or platelet derived growth factor (PDGF)-receptors in cell lysates, and bound synergistically to activated receptors when expressed together as one bacterial protein. In vitro complex formation was dependent on prior growth factor stimulation and was competed by intracellular PLC gamma 1. Similar results were obtained for binding of GAP SH2 domains to the PDGF-receptor. The isolated SH2 domains of other signaling proteins, such as p60src and Crk, also bound activated PDGF-receptors in vitro. SH2 domains, therefore, provide a common mechanism by which enzymatically diverse regulatory proteins can physically associate with the same activated receptors and thereby couple growth factor stimulation to intracellular signal transduction pathways.
Anderson
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Division of Molecular and Developmental Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Koch
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CA
Grey
L
L
Ellis
C
C
Moran
M F
MF
Pawson
T
T
D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D020690:GTPase-Activating Proteins; D016391:Genes, src / Q000235:genetics*; D010766:Phosphorylation; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor; D012689:Sequence Homology, Nucleic Acid; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism*
D020690:GTPase-Activating Proteins; D011506:Proteins; D011956:Receptors, Cell Surface; D066246:ErbB Receptors; D017479:Receptors, Platelet-Derived Growth Factor; D010738:Type C Phospholipases