Structural Basis for the Interaction between Pyk2-FAT Domain and Leupaxin LD Repeats

Vanarotti, Murugendra S.; Finkelstein, David B.; Guibao, Cristina D.; Nourse, Amanda; Miller, Darcie J.; Zheng, Jie J.

doi:10.1021/acs.biochem.5b01274

Title: Structural Basis for the Interaction between Pyk2-FAT Domain and Leupaxin LD Repeats

Journal Article · Wed Feb 24 00:00:00 EST 2016 · Biochemistry

DOI:https://doi.org/10.1021/acs.biochem.5b01274· OSTI ID:1248425

Vanarotti, Murugendra S.; Finkelstein, David B.; Guibao, Cristina D.; Nourse, Amanda; Miller, Darcie J.; Zheng, Jie J. ^[1]

Stein Eye Institute, Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, United States

Proline-rich tyrosine kinase 2 (Pyk2) is a nonreceptor tyrosine kinase and belongs to the focal adhesion kinase (FAK) family. Like FAK, the C-terminal focal adhesion-targeting (FAT) domain of Pyk2 binds to paxillin, a scaffold protein in focal adhesions; however, the interaction between the FAT domain of Pyk2 and paxillin is dynamic and unstable. Leupaxin is another member in the paxillin family and was suggested to be the native binding partner of Pyk2; Pyk2 gene expression is strongly correlated with that of leupaxin in many tissues including primary breast cancer. Here, we report that leupaxin interacts with Pyk2-FAT. Leupaxin has four leucine–aspartate (LD) motifs. The first and third LD motifs of leupaxin preferably target the two LD-binding sites on the Pyk2-FAT domain, respectively. Moreover, the full-length leupaxin binds to Pyk2-FAT as a stable one-to-one complex. Together, we propose that there is an underlying selectivity between leupaxin and paxillin for Pyk2, which may influence the differing behavior of the two proteins at focal adhesion sites.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: W-31-109-Eng-38; GM100909; CA21765; W-31-109- Eng-38

OSTI ID:: 1248425

Alternate ID(s):: OSTI ID: 1247366

Journal Information:: Biochemistry, Journal Name: Biochemistry Vol. 55 Journal Issue: 9; ISSN 0006-2960

Publisher:: American Chemical SocietyCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 13 works

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