3RZ2

Crystal of Prl-1 complexed with peptide

Summary for 3RZ2

• Entry DOI: 10.2210/pdb3rz2/pdb
• Descriptor: Protein tyrosine phosphatase type IVA 1, Prl-1 (PTP4A1) (3 entities in total)
• Functional Keywords: tyrosine phosphatase, prl-1, dual specific phosphatase, complexed with peptide, hydrolase
• Biological source: Rattus norvegicus (rat)
• Cellular location: Cell membrane : Q78EG7
• Total number of polymer chains: 4
• Total formula weight: 46061.29

Authors

Zhang, Z.-Y.,Liu, D.,Bai, Y. (deposition date: 2011-05-11, release date: 2011-10-26, Last modification date: 2024-11-06)

Primary citation

Bai, Y.,Luo, Y.,Liu, S.,Zhang, L.,Shen, K.,Dong, Y.,Walls, C.D.,Quilliam, L.A.,Wells, C.D.,Cao, Y.,Zhang, Z.Y.
PRL-1 protein promotes ERK1/2 and RhoA protein activation through a non-canonical interaction with the Src homology 3 domain of p115 Rho GTPase-activating protein.
J.Biol.Chem., 286:42316-42324, 2011

PubMed Abstract: Phosphatases of the regenerating liver (PRL) play oncogenic roles in cancer development and metastasis. Although previous studies indicate that PRL-1 promotes cell growth and migration by activating both the ERK1/2 and RhoA pathways, the mechanism by which it activates these signaling events remains unclear. We have identified a PRL-1-binding peptide (Peptide 1) that shares high sequence identity with a conserved motif in the Src homology 3 (SH3) domain of p115 Rho GTPase-activating protein (GAP). p115 RhoGAP directly binds PRL-1 in vitro and in cells via its SH3 domain. Structural analyses of the PRL-1·Peptide 1 complex revealed a novel protein-protein interaction whereby a sequence motif within the PxxP ligand-binding site of the p115 RhoGAP SH3 domain occupies a folded groove within PRL-1. This prevents the canonical interaction between the SH3 domain of p115 RhoGAP and MEKK1 and results in activation of ERK1/2. Furthermore, PRL-1 binding activates RhoA signaling by inhibiting the catalytic activity of p115 RhoGAP. The results demonstrate that PRL-1 binding to p115 RhoGAP provides a coordinated mechanism underlying ERK1/2 and RhoA activation.

PubMed: 22009749
DOI: 10.1074/jbc.M111.286302

Experimental method

X-RAY DIFFRACTION (2.8 Å)