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PAK promotes morphological changes by acting upstream of Rac
A Obermeier1, S Ahmed, E Manser
1Glaxo-IMCB Group, Institute of Molecular and Cell Biology, Singapore.
The EMBO Journal
|August 4, 1998
Summary
The serine/threonine kinase p21-activated kinase (PAK) acts upstream of Rac to promote cell shape changes. PAK
Area of Science:
- Cell Biology
- Molecular Biology
- Neuroscience
Background:
- The serine/threonine kinase p21-activated kinase (PAK) is a downstream effector of small GTPases Rac and Cdc42.
- While Rac and Cdc42 induce morphological changes, PAK's specific role remains unclear.
Purpose of the Study:
- To investigate the role of PAK in mediating Rac-induced cellular morphology.
- To elucidate the specific domains and interactions of PAK involved in lamellipodia formation.
Main Methods:
- Overexpression of betaPAK and its mutants in PC12 cells.
- Utilizing dominant-negative RacN17 to inhibit Rac activity.
- Employing a specific N-terminal PAK fragment to block PAK-PIX interaction.
Main Results:
- Overexpression of betaPAK induced a Rac phenotype, including cell spreading and lamellipodia formation.
- These effects were independent of PAK's kinase and p21-binding domains.
- Lamellipodia formation was inhibited by dominant-negative RacN17 and by blocking PAK-PIX interaction.
Conclusions:
- PAK acts upstream of Rac to mediate lamellipodia formation.
- PAK's N-terminal non-catalytic domain is crucial for this interaction with PIX.
- This pathway highlights a novel mechanism in regulating cell morphology.