Related Researcher

Author's Photo

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


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

Cited 6 times inthomson ciCited 5 times inthomson ci
Regulation of phospholipase C-gamma l by protein kinase A-dependent phosphorylation
Bae, SSChoi, Jang HyunOh, YSYun, SURyu, SHSuh, Pann-Ghill
Issue Date
Elsevier BV
Advances in Enzyme Regulation, v.42, pp.195 - 211
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.
Appears in Collections:
BIO_Journal Papers
Files in This Item:
There are no files associated with this item.

find_unist can give you direct access to the published full text of this article. (UNISTARs only)

Show full item record


  • mendeley


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.