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A new link between the c-Abl tyrosine kinase and phosphoinositide signalling through PLC-gamma1.

Publication ,  Journal Article
Plattner, R; Irvin, BJ; Guo, S; Blackburn, K; Kazlauskas, A; Abraham, RT; York, JD; Pendergast, AM
Published in: Nat Cell Biol
April 2003

The c-Abl tyrosine (Tyr) kinase is activated after platelet-derived-growth factor receptor (PDGFR) stimulation in a manner that is partially dependent on Src kinase activity. However, the activity of Src kinases alone is not sufficient for activation of c-Abl by PDGFR. Here we show that functional phospholipase C-gamma1 (PLC-gamma1) is required for c-Abl activation by PDGFR. Decreasing cellular levels of phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) by PLC-gamma1-mediated hydrolysis or dephosphorylation by an inositol polyphosphate 5-phosphatase (Inp54) results in increased Abl kinase activity. c-Abl functions downstream of PLC-gamma1, as expression of kinase-inactive c-Abl blocks PLC-gamma1-induced chemotaxis towards PDGF-BB. PLC-gamma1 and c-Abl form a complex in cells that is enhanced by PDGF stimulation. After activation, c-Abl phosphorylates PLC-gamma1 and negatively modulates its function in vivo. These findings uncover a newly discovered functional interdependence between non-receptor Tyr kinase and lipid signalling pathways.

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Published In

Nat Cell Biol

DOI

ISSN

1465-7392

Publication Date

April 2003

Volume

5

Issue

4

Start / End Page

309 / 319

Location

England

Related Subject Headings

  • Type C Phospholipases
  • Signal Transduction
  • Recombinant Fusion Proteins
  • Receptor, Platelet-Derived Growth Factor beta
  • Proto-Oncogene Proteins c-abl
  • Protein Structure, Tertiary
  • Platelet-Derived Growth Factor
  • Phosphorylation
  • Phospholipase C gamma
  • Phosphatidylinositol 4,5-Diphosphate
 

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Plattner, R., Irvin, B. J., Guo, S., Blackburn, K., Kazlauskas, A., Abraham, R. T., … Pendergast, A. M. (2003). A new link between the c-Abl tyrosine kinase and phosphoinositide signalling through PLC-gamma1. Nat Cell Biol, 5(4), 309–319. https://doi.org/10.1038/ncb949
Plattner, Rina, Brenda J. Irvin, Shuling Guo, Kevin Blackburn, Andrius Kazlauskas, Robert T. Abraham, John D. York, and Ann Marie Pendergast. “A new link between the c-Abl tyrosine kinase and phosphoinositide signalling through PLC-gamma1.Nat Cell Biol 5, no. 4 (April 2003): 309–19. https://doi.org/10.1038/ncb949.
Plattner R, Irvin BJ, Guo S, Blackburn K, Kazlauskas A, Abraham RT, et al. A new link between the c-Abl tyrosine kinase and phosphoinositide signalling through PLC-gamma1. Nat Cell Biol. 2003 Apr;5(4):309–19.
Plattner, Rina, et al. “A new link between the c-Abl tyrosine kinase and phosphoinositide signalling through PLC-gamma1.Nat Cell Biol, vol. 5, no. 4, Apr. 2003, pp. 309–19. Pubmed, doi:10.1038/ncb949.
Plattner R, Irvin BJ, Guo S, Blackburn K, Kazlauskas A, Abraham RT, York JD, Pendergast AM. A new link between the c-Abl tyrosine kinase and phosphoinositide signalling through PLC-gamma1. Nat Cell Biol. 2003 Apr;5(4):309–319.

Published In

Nat Cell Biol

DOI

ISSN

1465-7392

Publication Date

April 2003

Volume

5

Issue

4

Start / End Page

309 / 319

Location

England

Related Subject Headings

  • Type C Phospholipases
  • Signal Transduction
  • Recombinant Fusion Proteins
  • Receptor, Platelet-Derived Growth Factor beta
  • Proto-Oncogene Proteins c-abl
  • Protein Structure, Tertiary
  • Platelet-Derived Growth Factor
  • Phosphorylation
  • Phospholipase C gamma
  • Phosphatidylinositol 4,5-Diphosphate