
與 Phactr1/PP1 全酶不同，Neurabin/PP1 全酶的受質特異性主要由與 Neurabin PDZ 結合域的交互作用決定，而不是由去磷酸化位點本身的初級序列決定。


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Protein Phosphatase 1 (PP1) relies on association with PP1-interacting proteins (PIPs) to generate substrate-specific PIP/PP1 holoenzymes, but the lack of well-defined substrates has hindered elucidation of the mechanisms involved. We previously demonstrated that the Phactr1 PIP confers sequence specificity on the Phactr1/PP1 holoenzyme by remodelling the PP1 hydrophobic substrate groove. Phactr1 defines a group of “RVxF-ΦΦ-R-W” PIPs that all interact with PP1 in a similar fashion. Here we use a PP1-PIP fusion approach to address sequence specificity and identify substrates of the RVxF-ΦΦ-R-W family PIPs. We show that the four Phactr proteins confer identical sequence specificities on their holoenzymes. We identify the 4E-BP and p70 S6K translational regulators as substrates for the Neurabin/Spinophilin PIPs, implicated in neuronal plasticity, pointing to a role for their holoenzymes in mTORC1-dependent translational control. Biochemical and structural experiments show that in contrast to the Phactrs, substrate recruitment and catalytic efficiency of the PP1-Neurabin and PP1-Spinophilin fusions is primarily determined by substrate interaction with the PDZ domain adjoining their RVxF-ΦΦ-R-W motifs, rather than by recognition of the remodelled PP1 hydrophobic groove. Thus, even PIPs that interact with PP1 in a similar manner use different mechanisms to ensure substrate selectivity.

### Competing Interest Statement

The authors have declared no competing interest.

PDZ-directed substrate recruitment is the primary determinant of specific 4E-BP1 dephosphorylation by PP1-Neurabin

由-pp1-neurabin-介導的-pdz-定向受質募集是特定-4e-bp1-去磷酸化的主要決定因素


由 PP1-Neurabin 介導的 PDZ 定向受質募集是特定 4E-BP1 去磷酸化的主要決定因素
