jcb_24108_sm_SupplTabS4

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Table SIV: Summary of interactions between B23 and each predicted kinase. The interactions were defined as direct or indirect according to the interaction database STRING 8.2 (Jensen et al., 2009) (http://string-db.org/).

Direct Interactions (DI): the experimentally determined physical contacts, including phosphorylation (von

Mering et al., 2005).

Phoshorylation column: each (+) symbol represents one experimentally verified phosphosite. Physical Interactions column: each (+) symbol represents one interaction site or region of B23 with the kinase. Indirect Interactions (IDI): considered the subcellular localization, the cellular processes and signaling pathways shared by B23 and each predicted kinase or the genes encoding these proteins (Jensen et al., 2009;von Mering et al., 2005;Ideker and Sharan, 2008), as well as the protein-protein interaction networks in which B23 and each kinase are connected by shared components (Gagneur et al., 2004).

Subcellular Localization column: each (+) symbol represents a subcellular localization. Cellular Processes,

Signaling Pathways and Networks columns: each (+) symbol refer to each one of these events that involve

B23 and each predicted kinase. The parameter P represents the probability that each predicted kinase interacts and phosphorylates B23 calculated as described in M&M. More detailed information concerning these interactions is available in Supplementary Material Table SIII.

Kinase

Symbols

CK2

CDK

PKC

PKA

MAPK

CK1

ATM

PLK

RSK

STK4

CHK1

GRK

PKG

PSK3

Aurora

PKB

PDK

IKK

MAPKAPK2

CaM

GSK3

FGR

RET

EPH

Direct Interaction (DI)

Phosphorylation Physical

Interactions

Indirect Interactions (IDI)

Subcellular

Localization

Cellular processes

Signaling

Pathways

+

++++

+

+

++

+++

++

+

+

+

Total of interactions

Networks Total (T)

T = DI +

IDI

+

+

8

13

(P)

P =T/13

0.62

1

++

+

+

+

+ ++

++

+++

+++

+++

+++

+

+++++

++++

+++

++++

++

+++

++

+

+

+

+

+

+

+

7

9

10

9

9

8

0.69

0.69

0.62

0.54

0.69

0.77

+

+++ + ++ 7 0.54

+

+

+

++

+++

++

+

+++

+++

++

++

++

+

+++

+++

+

+

+++

+

+

+

+

+

+

+

3

7

13

5

8

4

3

0.38

0.62

0.31

0.23

0.23

0.54

1

++

++

++

++

++

+++

+

++++

+

+

++++

+

+

++++

+++

+

++

+++

+

+

+

+

+

11

7

4

2

10

1

5

2

0.85

0.54

0.31

0.15

0.77

0.08

0.38

0.15

IRR

SRC

TYK2

INSR

FGFR1

ALK

PDGFR

+

++

+++

+

+

+

+

+

++

++

+

+

+

+

1

4

6

1

4

2

1

0.08

0.31

0.46

0.08

0.31

0.15

0.08

JAK2

IGFIR

ZAP70

BTK

++

+++

++

++

++

++

+

+

+

+

5

5

3

3

0.38

0.38

0.23

0.23

FES

Direct Interaction (DI)

++

Indirect Interactions (IDI)

3 0.23

Total interactions i Light grey rows represent kinases with a number of interactions higher than or equal to that of CK2, the kinase that has been experimentally verified to phosphorylate B23 with the lowest number of interactions (eigth). Therefore, P

CK2

(0.62) is the significant limit of P.

Reference List

1. Frezal,J. 1998. Genatlas database, genes and development defects. C. R. Acad. Sci. III 321:805-817.

2. Gagneur,J., Krause,R., Bouwmeester,T., and Casari,G. 2004. Modular decomposition of protein-protein interaction networks. Genome Biol. 5:R57.

3. Gasteiger,E., Gattiker,A., Hoogland,C., Ivanyi,I., Appel,R.D., and Bairoch,A. 2003. ExPASy: The proteomics server for in-depth protein knowledge and analysis. Nucleic Acids Res. 31:3784-3788.

4. Ideker,T., and Sharan,R. 2008. Protein networks in disease. Genome Res. 18:644-652.

5. Jensen,L.J., Kuhn,M., Stark,M., Chaffron,S., Creevey,C., Muller,J., Doerks,T., Julien,P., Roth,A.,

Simonovic,M., Bork,P., and von,M.C. 2009. STRING 8--a global view on proteins and their functional interactions in 630 organisms. Nucleic Acids Res. 37:D412-D416.

6. Kanehisa,M., Araki,M., Goto,S., Hattori,M., Hirakawa,M., Itoh,M., Katayama,T., Kawashima,S., Okuda,S.,

Tokimatsu,T., and Yamanishi,Y. 2008. KEGG for linking genomes to life and the environment.

Nucleic Acids Res. 36:D480-D484.

7. Safran,M., Solomon,I., Shmueli,O., Lapidot,M., Shen-Orr,S., Adato,A., Ben-Dor,U., Esterman,N., Rosen,N.,

Peter,I., Olender,T., Chalifa-Caspi,V., and Lancet,D. 2002. GeneCards 2002: towards a complete, object-oriented, human gene compendium. Bioinformatics. 18:1542-1543.

8. von Mering,C., Jensen,L.J., Snel,B., Hooper,S.D., Krupp,M., Foglierini,M., Jouffre,N., Huynen,M.A., and

Bork,P. 2005. STRING: known and predicted protein-protein associations, integrated and transferred across organisms. Nucleic Acids Res. 33:D433-D437.

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