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Suh, Pann-Ghill
BioSignal Network Lab (BSN)
Research Interests
  • Signal transduction, cancer, metabolism, phospholipase C

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Regulation of phospholipase C-gamma l by protein kinase A-dependent phosphorylation

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Title
Regulation of phospholipase C-gamma l by protein kinase A-dependent phosphorylation
Author
Bae, SSChoi, Jang HyunOh, YSYun, SURyu, SHSuh, Pann-Ghill
Issue Date
2002
Publisher
Elsevier BV
Citation
Advances in Enzyme Regulation, v.42, pp.195 - 211
Abstract
Phospholipase C-γ1 (PLC-γ1) is activated by growth factor receptors through phosphorylation at tyrosine residues. Using phospho-specific antibodies, we have discovered that Ser 1248 is phosphorylated by epidermal growth factor (EGF) and platelet-derived growth factor (PDGF), but not by insulin. Phosphorylation state of PLC-γ1 at Ser 1248 was not affected by transient expression of Akt, Ras, and Raf kinases. Moreover, PI3K inhibitor (LY294002) and MEK inhibitor (PD98059) did not affect EGF-induced phosphorylation at Ser 1248 of PLC-γ1. Elevation of intracellular cAMP level by treating COS-7 cells with isobutylmethylxanthine (IBMX) and forskolin considerably induced PLC-γ1 phosphorylation at Ser 1248. Furthermore, pretreatment with protein kinase A (PKA) inhibitor completely abolished EGF-induced phosphorylation at Ser 1248 of PLC-γ1. These results indicate that PKA phosphorylates Ser 1248 of PLC-γ1. Stimulation of COS-7 cells with β2-adrenergic receptor agonist, Isoproterenol, induced phosphorylation at Ser 1248 of PLC-γ1. Isoproterenol-induced phosphorylation at Ser 1248 was completely abolished by pretreatment of cells with antagonist such as Propanolol. However, Propanolol could not inhibit EGF-induced Ser 1248 phosphorylation of PLC-γ1, indicating that EGF receptor activates downstream signaling molecules rather than β2-adrenergic receptor itself. Phosphorylation at Ser 1248 was abolished by the deletion of SH2 domains of PLC-γ1. In addition, mutation at Tyr 1254 did not cause phosphorylation at Ser 1248 by treatment with EGF. These results suggest that recruitment to the receptor tyrosine kinase and phosphorylation at Tyr 1254 are the prerequisites for the subsequent phosphorylation at Ser 1248 of PLC-γ1. Finally, mutation at Ser 1248 of PLC-γ1 resulted in the elevation of EGF-induced PLC activity. This indicates that Ser 1248 of PLC-γ1 is phosphorylated through a mechanism dependent on EGF-induced PKA activation. PLC-γ1 may be negatively regulated through the subsequent phosphorylation at Ser 1248 by PKA, which is activated by either growth factor receptor or G-protein coupled receptor.
URI
https://scholarworks.unist.ac.kr/handle/201301/7291
URL
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0036374272
DOI
10.1016/S0065-2571(01)00031-0
ISSN
0065-2571
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BIO_Journal Papers
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