Transmodulation between phospholipase D and c-Src enhances cell proliferation

Bong Hyun Ahn, Shi Yeon Kim, Eun Hee Kim, Kyeong Sook Choi, Taeg Kyu Kwon, Young Han Lee, Jong Soo Chang, Myung Suk Kim, Yang Hyeok Jo, Do Sik Min

Research output: Contribution to journalArticlepeer-review

82 Citations (Scopus)

Abstract

Phospholipase D (PLD) has been implicated in the signal transduction pathways initiated by several mitogenic protein tyrosine kinases. We demonstrate for the first time that most notably PLD2 and to a lesser extent the PLD1 isoform are tyrosine phosphorylated by c-Src tyrosine kinase via direct association. Moreover, epidermal growth factor induced tyrosine phosphorylation of PLD2 and its interaction with c-Src in A431 cells. Interaction between these proteins is via the pleckstrin homology domain of PLD2 and the catalytic domain of c-Src. Coexpression of PLD1 or PLD2 with c-Src synergistically enhances cellular proliferation compared with expression of either molecule. While PLD activity as a lipid-hydrolyzing enzyme is not affected by c-Src, wild-type PLDs but not catalytically inactive PLD mutants significantly increase c-Src kinase activity, up-regulating c-Src-mediated paxillin phosphorylation and extracellular signal-regulated kinase activity. These results demonstrate the critical role of PLD catalytic activity in the stimulation of Src signaling. In conclusion, we provide the first evidence that c-Src acts as a kinase of PLD and PLD acts as an activator of c-Src. This transmodulation between c-Src and PLD may contribute to the promotion of cellular proliferation via amplification of mitogenic signaling pathways.

Original languageEnglish
Pages (from-to)3103-3115
Number of pages13
JournalMolecular and cellular biology
Volume23
Issue number9
DOIs
Publication statusPublished - 2003 May

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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