Pyk2 regulates cell-edge protrusion dynamics by interacting with Crk

Nikola Lukic, Stefanie Lapetina, Hanna Grobe, Kolluru D. Srikanth, Shams Twafra, Jonathan Solomon, Tal Sneh, Michal Gendler, Ronen Zaidel-Bar, Hava Gil-Henn

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2 Scopus citations


Focal adhesion kinase (FAK) is well established as a regulator of cell migration, but whether and how the closely related proline-rich tyrosine kinase 2 (Pyk2) regulates fibroblast motility is still under debate. Using mouse embryonic fibroblasts (MEFs) from Pyk2-/- mice, we show here, for the first time, that lack of Pyk2 significantly impairs both random and directed fibroblast motility. Pyk2-/- MEFs show reduced cell-edge protrusion dynamics, which is dependent on both the kinase and protein-protein binding activities of Pyk2. Using bioinformatics analysis of in vitro high- throughput screens followed by text mining, we identified CrkI/II as novel substrates and interactors of Pyk2. Knockdown of CrkI/II shows altered dynamics of cell-edge protrusions, which is similar to the phenotype observed in Pyk2-/- MEFs. Moreover, epistasis experiments suggest that Pyk2 regulates the dynamics of cell-edge protrusions via direct and indirect interactions with Crk that enable both activation and down-regulation of Crk-mediated cytoskeletal signaling. This complex mechanism may enable fine-tuning of cell-edge protrusion dynamics and consequent cell migration on the one hand together with tight regulation of cell motility, a process that should be strictly limited to specific time and context in normal cells, on the other hand.

Original languageEnglish
Article number0640
JournalMolecular Biology of the Cell
Issue number21
StatePublished - 1 Nov 2021

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© 2021 Lukic et al.


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