PROTEIN TYROSINE PHOSPHATASE 1B, PTP1B, TARGETS FAK AND PAXILLIN IN CELL-MATRIX ADHESIONS

ANA E. GONZÁLEZ WUSENER; ANGELA GONZALEZ; MARIA EUGENIA PEREZ COLLADO; MELINA R. MAZA; IGNACIO J. GENERAL; ARREGUI, CARLOS O

JOURNAL OF CELL SCIENCE

COMPANY OF BIOLOGISTS LTD

Lugar: Cambridge; Año: 2021

0021-9533

Protein tyrosine phosphatase 1B (PTP1B) is an established regulator of cell-matrixadhesion and motility. However, the nature of substrate targets at adhesion sites remains tobe validated. Here we used Bimolecular Fluorescence Complementation (BiFC) assays incombination with a substrate trapping mutant of PTP1B to directly examine whetherrelevant phosphotyrosines on paxillin and FAK are substrates of the phosphatase in thecontext of cell-matrix adhesion sites. We find that formation of catalytic complexes at cell-matrix adhesions requires intact tyrosine residues Y31 and Y118 on paxillin and thelocalization of the focal adhesion kinase (FAK) at adhesion sites. In addition, we find thatPTP1B specifically targets the Y925 on the focal adhesion target (FAT) domain of FAK atadhesion sites. Electrostatic analysis indicates that dephosphorylation of this residuepromotes the closed conformation of the FAT 4-helix bundle, and its interaction withpaxillin at adhesion sites.