Regulation von Chemotaxis durch Phosphoinositid 3-Kinasen in Leukozyten

• Applicant: Dr. Lutz Zeitlmann
• Subject Area: Cell Biology
• Term: from 2001 to 2004
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5321286

Directed cellular migration along gradients of chemoattractant (chemotaxis) represents a highly integrative cellular process, the detailed analysis of which should allow insights into various aspects of intracellular signal transduction. In addition to heterotrimeric G-proteins, protein tyrosine kinases, serine/threonine kinases, phospholipases and small G-proteins of the rho-family have been implicated in the establishment of cellular polarity and motility. Recently, the G-protein-coupled gamma-isoform of the phosphoinositide 3-kinase (PI 3-Kg) was identified as a principal effector of heterotrimeric G-proteins in this functional context. The local activation of PI 3-kinase activity by a concentration gradient of chemoattractant results in a massive accumulation of the phospholipid phosphatidylinositol (3,4,5)-trisphosphate (PIP3) at one pole of the cell. The experiments proposed in this grant application should allow the identification of cellular effectors, which serve to translate this asymmetric accumulation of PIP3 into cellular polarity and migration. A detailed understanding of these processes in various cell types would provide diverse possibilities for pharmacological intervention.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1111: Cell Polarity
• International Connection: USA
• Participating Person: Professor Dr. Henry R. Bourne