Aufgrund von Vorbereitungen auf eine neue Version von KOPS, können am Montag, 6.2. und Dienstag, 7.2. keine Publikationen eingereicht werden. (Due to preparations for a new version of KOPS, no publications can be submitted on Monday, Feb. 6 and Tuesday, Feb. 7.)
Type of Publication: | Journal article |
URI (citable link): | http://nbn-resolving.de/urn:nbn:de:bsz:352-opus-41320 |
Author: | Klingbeil, Candice K.; Hauck, Christof R.; Hsia, Datsun A.; Reider, Shannon R.; Jones, K. C.; Schlaepfer, David D. |
Year of publication: | 2001 |
Published in: | Journal of Cell Biology ; 152 (2001), 1. - pp. 97-110. - ISSN 0021-9525. - eISSN 1540-8140 |
DOI (citable link): | https://dx.doi.org/10.1083/jcb.152.1.97 |
Summary: |
Focal adhesion kinase null (FAK-/-) fibroblasts exhibit morphological and motility defects that are reversed by focal adhesion kinase (FAK) reexpression. The FAK-related kinase, proline-rich tyrosine kinase 2 (Pyk2), is expressed in FAK-/- cells, yet it exhibits a perinuclear distribution and does not functionally substitute for FAK. Chimeric Pyk2/FAK proteins were created and expressed in FAK-/- cells to determine the impact of Pyk2 localization to focal contacts. Whereas an FAK/Pyk2 COOH-terminal (CT) domain chimera was perinuclear distributed, stable expression of a Pyk2 chimera with the FAK-CT domain (Pyk2/FAK-CT) localized to focal contact sites and enhanced fibronectin (FN)-stimulated haptotactic cell migration equal to FAK-reconstituted cells. Disruption of paxillin binding to the FAK-CT domain (S-1034) inhibited Pyk2/FAK-CT localization to focal contacts and its capacity to promote cell motility. Paxillin binding to the FAK-CT was necessary but not sufficient to mediate the indirect association of FAK or Pyk2/FAK-CT with a ß1-integrin containing complex. Both FAK and Pyk2/FAK-CT but not Pyk2/FAK-CT S-1034 reconstituted FAK-/- cells, exhibit elevated FN-stimulated extracellular signal regulated kinase 2 (ERK2) and c-Jun NH2-terminal kinase (JNK) kinase activation. FN-stimulated FAK or Pyk2/FAK-CT activation enhanced both the extent and duration of FN-stimulated ERK2 activity which was necessary for cell motility. Transient overexpression of the FAK-CT but not FAK-CT S-1034 domain inhibited both FN-stimulated ERK2 and JNK activation as well as FN-stimulated motility of Pyk2/FAK-CT reconstituted cells. These gain-of-function studies show that the NH2-terminal and kinase domains of Pyk2 can functionally substitute for FAK in promoting FN-stimulated signaling and motility events when localized to ß-integrin containing focal contact sites via interactions mediated by the FAK-CT domain.
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Subject (DDC): | 570 Biosciences, Biology |
Keywords: | FAK, Pyk2, cell migration, integrins, signaling |
Link to License: | Attribution-NonCommercial-NoDerivs 2.0 Generic |
KLINGBEIL, Candice K., Christof R. HAUCK, Datsun A. HSIA, Shannon R. REIDER, K. C. JONES, David D. SCHLAEPFER, 2001. Targeting Pyk2 to Beta1-Integrin containing Focal Contacts Rescues Fibronectin stimulated Signaling and Haptotactic Motility Defects of Focal Adhesion Kinase null Cells. In: Journal of Cell Biology. 152(1), pp. 97-110. ISSN 0021-9525. eISSN 1540-8140. Available under: doi: 10.1083/jcb.152.1.97
@article{Klingbeil2001Targe-8752, title={Targeting Pyk2 to Beta1-Integrin containing Focal Contacts Rescues Fibronectin stimulated Signaling and Haptotactic Motility Defects of Focal Adhesion Kinase null Cells}, year={2001}, doi={10.1083/jcb.152.1.97}, number={1}, volume={152}, issn={0021-9525}, journal={Journal of Cell Biology}, pages={97--110}, author={Klingbeil, Candice K. and Hauck, Christof R. and Hsia, Datsun A. and Reider, Shannon R. and Jones, K. C. and Schlaepfer, David D.} }
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Targeting_Pyk2.pdf | 764 |