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  A kindlin-3-leupaxin-paxillin signaling pathway regulates podosome stability

Klapproth, S., Bromberger, T., Tuerk, C., Krueger, M., & Moser, M. (2019). A kindlin-3-leupaxin-paxillin signaling pathway regulates podosome stability. JOURNAL OF CELL BIOLOGY, 218(10), 3436-3454. doi:10.1083/jcb.201903109.

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Genre: Journal Article

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 Creators:
Klapproth, Sarah1, Author              
Bromberger, Thomas1, Author              
Tuerk, Clara2, Author
Krueger, Marcus2, Author
Moser, Markus1, Author              
Affiliations:
1Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565147              
2external, ou_persistent22              

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Free keywords: FOCAL ADHESION; TYROSINE PHOSPHORYLATION; PTP-PEST; INTEGRIN ACTIVATION; STRUCTURAL BASIS; ADAPTER PROTEIN; ILK-COMPLEX; PAXILLIN; LEUPAXIN; KINDLINCell Biology;
 Abstract: Binding of kindlins to integrins is required for integrin activation, stable ligand binding, and subsequent intracellular signaling. How hematopoietic kindlin-3 contributes to the assembly and stability of the adhesion complex is not known. Here we report that kindlin-3 recruits leupaxin into podosomes and thereby regulates paxillin phosphorylation and podosome turnover. We demonstrate that the activity of the protein tyrosine phosphatase PTP-PEST, which controls paxillin phosphorylation, requires leupaxin. In contrast, despite sharing the same binding mode with leupaxin, paxillin recruitment into podosomes is kindlin-3 independent. Instead, we found paxillin together with talin and vinculin in initial adhesion patches of kindlin-3-null cells. Surprisingly, despite its presence in these early adhesion patches, podosomes can form in the absence of paxillin or any paxillin member. In conclusion, our findings show that kindlin-3 not only activates and clusters integrins into podosomes but also regulates their lifetime by recruiting leupaxin, which controls PTP-PEST activity and thereby paxillin phosphorylation and downstream signaling.

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Language(s): eng - English
 Dates: 2019
 Publication Status: Published in print
 Pages: 19
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000489119800021
DOI: 10.1083/jcb.201903109
 Degree: -

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Title: JOURNAL OF CELL BIOLOGY
Source Genre: Journal
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Publ. Info: 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA : ROCKEFELLER UNIV PRESS
Pages: - Volume / Issue: 218 (10) Sequence Number: - Start / End Page: 3436 - 3454 Identifier: ISSN: 0021-9525