INT1941

Context Info Confidence 0.48 First Reported 1977 Last Reported 2009 Negated 2 Speculated 2 Reported most in Body Documents 36 Total Number 38 Disease Relevance 5.92 Pain Relevance 1.16

cytosol (PSTPIP1) signal transduction (PSTPIP1) oxidoreductase activity (PSTPIP1) cell adhesion (PSTPIP1) cytoskeleton (PSTPIP1) cytoplasm (PSTPIP1)

Anatomy Link Frequency filaments 6 SH3 5 tubules 1 mononuclear cells 1 PSTPIP1 (Homo sapiens) PSTPIP1 - W232A (1)

Pain Link Frequency Relevance Heat Inflammation 339 99.24 Multiple sclerosis 65 98.56 Arthritis 70 90.76 Fibrositis 97 90.20 Central nervous system 4 89.32 palliative 1 85.04 chemokine 17 83.04 cytokine 16 62.80 Stimulus evoked pain 1 42.84 COX2 1 38.24

Disease Link Frequency Relevance Heat Syndrome 322 99.72 Disease 372 99.50 INFLAMMATION 341 99.24 Fever 388 99.20 Cancer 5 98.70 Multiple Sclerosis 69 98.56 Familial Mediterranean Fever 25 95.76 Acne 70 92.04 Pyoderma Gangrenosum 70 91.64 Arthritis 70 90.76

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

First, our studies show clearly that the SH3 domain of PSTPIP1 is not required for pyrin binding nor is it necessary for pyrin-mediated reticularization of PSTPIP1 filaments.

PSTPIP1 Binding (binding) of in filaments

1) Confidence 0.48 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0.05 Pain Relevance 0.03

The results of these analyses suggest a revised model of pyrin/PSTPIP interaction in the context of inflammatory disease.

PSTPIP Binding (interaction) of associated with inflammation and disease

2) Confidence 0.48 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0.20 Pain Relevance 0.05

We also examine the pyrin/PSTPIP1 interaction and show that contrary to earlier predictions [5], the PSTPIP1 SH3 domain is not required for its interaction with pyrin.

PSTPIP1 Spec (examine) Binding (interaction) of in SH3

3) Confidence 0.48 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0.21 Pain Relevance 0

We next examined smaller fragments of the pyrin molecule to determine which regions are required for PSTPIP1 binding and filament redistribution.

PSTPIP1 Binding (binding) of in filament

4) Confidence 0.48 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0 Pain Relevance 0

The model also suggests that the coherent convex binding surface would likely interact with both pyrin and the PEST phosphatases, since these PSTPIP1 mutations have been shown to reduce binding affinity for PEST phosphatases and increase affinity for pyrin (Shoham, 2005).

PEST Binding (affinity) of

5) Confidence 0.42 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0.07 Pain Relevance 0

PSTPIP1 filament formation in transfected cells: lack of requirement for the SH3 domain and effect of PAPA-associated mutations

PSTPIP1 Binding (formation) of in SH3

6) Confidence 0.37 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0 Pain Relevance 0

Finally, we directly test the binding relationships between PSTPIP1, pyrin, and the pyrin-binding protein ASC.

PSTPIP1 Binding (binding) of

7) Confidence 0.37 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0.38 Pain Relevance 0.04

PSTPIP1 filaments are lipid membrane associated

PSTPIP1 Binding (associated) of in filaments

8) Confidence 0.37 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0.09 Pain Relevance 0

Thus, the SH3 domain is apparently dispensable for the interaction between pyrin and PSTPIP1.

PSTPIP1 Binding (interaction) of in SH3

9) Confidence 0.37 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0 Pain Relevance 0

PSTPIP1 has previously been linked to the actin cytoskeleton [13], and we report an additional requirement for the tubulin cytoskeleton in generation of PSTPIP1 filamentous structure.

PSTPIP1 Binding (linked) of

10) Confidence 0.37 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0 Pain Relevance 0

Pyrin exons 2–4 produced a protein capable of aligning with PSTPIP1 filaments, but the PSTPIP1 filament network was not reticularized (Figure 5E–F).

PSTPIP1 Binding (aligning) of in filament

11) Confidence 0.37 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0.05 Pain Relevance 0

These data suggest that the PSTPIP1 pattern may arise from a direct or indirect association with microtubules.

PSTPIP1 Binding (association) of

12) Confidence 0.37 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0 Pain Relevance 0

Similarly, in previous studies using immunoprecipitation, mutations in pyrin did not modify its interaction with PSTPIP1 [5].

PSTPIP1 Neg (not) Binding (interaction) of

13) Confidence 0.37 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0.15 Pain Relevance 0

Finally, we examine the binding relationships between PSTPIP1, pyrin, and the pyrin-binding protein ASC.

PSTPIP1 Spec (examine) Binding (binding) of

14) Confidence 0.37 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0.18 Pain Relevance 0.04

To explore the effect of PAPA mutations on the PSTPIP1:pyrin interaction, we next tested whether the filaments formed by mutant forms of PSTPIP1 could be reorganized by pyrin.

PSTPIP1 Binding (interaction) of in filaments

15) Confidence 0.37 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0.15 Pain Relevance 0

Finally, we directly test the binding relationships between PSTPIP1, pyrin, and the pyrin-binding protein ASC.

PSTPIP1 Binding (binding) of

16) Confidence 0.37 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0.37 Pain Relevance 0.04

In the remaining cells, PSTPIP1 is not associated with specks (Figure 9K–P).

PSTPIP1 Binding (associated) of

17) Confidence 0.37 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0 Pain Relevance 0

Additionally, a mutation in the CC region of PSTPIP1, W232A, abolished PSTPIP1 binding both to pyrin [5] and to the PEST phosphatase, PTP-HSCF [8].

PSTPIP1 Binding (binding) of

18) Confidence 0.37 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0 Pain Relevance 0

Indeed, the F-BAR domains of both PSTPIP1 and PSTPIP2 can bind to artificial liposomes containing phosphatidyl inositol (4,5) bisphosphate (PI(4,5)P2) with high affinity [19].

PSTPIP1 Binding (bind) of

19) Confidence 0.37 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0 Pain Relevance 0

The binding of PSTPIP1 and pyrin was previously studied by immunoprecipitation and the SH3 domain of PSTPIP1 was found to be necessary but not sufficient for this interaction [5].

PSTPIP1 Binding (binding) of in SH3

20) Confidence 0.37 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0 Pain Relevance 0

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