Table 1. Top-ranked SFK candidate protein substrates and secondary targets based on correlated response to perturbations of SFK activity.
Observed phosphorylation events are ranked using the SFK perturbation response scores from Fig. 3A, and the top ranked events are listed along with their mouse (and human in parenthesis) phosphosite residue number. For each protein, only the top-scoring phosphopeptide sequence is listed. The complete results along with fold change values for all drug inhibition and kinase overexpression experiments can be found in table S3.
| Protein * | Phosphopeptide sequence | Phospho- site |
Protein description | SFK perturb. score |
estimated p-value † |
SFK interac- tion‡ |
|---|---|---|---|---|---|---|
| Was | LIpYDFIEDQGGLEAVR | Y293 (Y290) | Wiskott-Aldrich syndrome | 25.8 | 9.9E-09 (4.8E-06) |
substrate/ PPI |
| Ptpn18 | APTSTDTPIpYSQVAPR | Y381 (Y389) | protein tyrosine phosphatase, non- receptor type 18 |
17.2 | 3.0E-05 (1.5E-03) |
PPI |
| Fyb | TTAVEIDpYDSLKR | Y560 (Y571) | FYN binding protein | 17.0 | 2.3E-07 (3.7E-05) |
substrate/ PPI |
| Lyn | EEPIpYIITEYMAK | (Y316) § | Lyn (Src family kinase) | 16.2 | 1.5E-07 (3.5E-05) |
|
| Lyn | EEPIpYIITEFMAK | Y316 (Y316) | Lyn (Src family kinase) | 15.2 | 1.0E-06 (1.2E-04) |
|
| Hck | TLDNGGFpYISPR | (Y187) § | hemopoietic cell kinase | 14.7 | 2.0E-06 (1.6E-04) |
|
| Btk | KVVALYDpYMPMNANDLQLR | Y224 (Y224) | Bruton agammaglobulinemia tyrosine kinase |
14.4 | 1.7E-05 (1.0E-03) |
substrate/ PPI |
| Pag1 | AADTELGPGVEGPpYEVLK | Y165 (Y163) | phosphoprotein associated with glycosphingolipid microdomains 1 |
13.3 | 1.9E-06 (1.9E-04) |
PPI |
| Dapp1 | EVEEPCIpYESVR | Y139 (Y139) | dual adaptor of phosphotyrosine and 3-phosphoinositides |
11.2 | 3.8E-05 (1.5E-03) |
substrate/ PPI |
| Itsn2 | GEPEALpYAAVTK | Y922 (Y941) | intersectin 2 | 11.1 | 3.0E-03 (3.9E-02) |
|
| Hsp90ab1 | LVSSPCCIVTSTpYGWTANMER | Y596 (Y596) | heat shock protein 90kDa alpha, class B member 1 |
10.5 | 1.4E-02 (9.4E-02) |
|
| Eno1 | GNPTVEVDLpYTAK | Y24 (F25) | enolase 1, (alpha) | 10.5 | 2.5E-03 (3.7E-02) |
|
| Cbl | VTQEQpYELYCEMGSTFQLCK | Y366 (Y368) | Cas-Br-M (murine) ecotropic retroviral transforming sequence |
10.5 | 1.7E-03 (3.2E-02) |
substrate/ PPI |
| Prkcd | KLDTTESVGIpYQGFEK | Y311 (Y313) | protein kinase C, delta | 10.3 | 1.9E-03 (3.3E-02) |
substrate/ PPI |
| Sgk269 | VPIVINPNAYDNLAIpYK | Y638 (Y641) | NKF3 kinase family member | 10.2 | 1.5E-03 (3.0E-02) |
|
| Actn1 | AIMTYVSSFpYHAFSGAQK | Y246 (Y246) | actinin, alpha 1 | 10.1 | 9.4E-03 (7.2E-02) |
|
| Dok2 | SGSPCMEENELpYSSSTTGLCK | Y142 (Y139) | docking protein 2 | 10.0 | 7.6E-03 (6.3E-02) |
PPI |
| Pxn | AGEEEHVpYSFPNK | Y118 (Y118) | paxillin | 9.6 | 5.3E-04 (1.4E-02) |
PPI |
Proteins indicated in bold are involved in SFK feedback mechanisms (Fig. 4).
Estimated p-values for the observed fold changes used to calculate the perturbation score are based on the like sample distributions in fig. S12. Values in parenthesis are Benjamini and Hochberg multiple hypothesis corrected.
The SFK interaction column indicates experimental evidence for SFK substrates and SFK protein-protein functional interactions (PPI) based on the HPRD database and is the basis for the enrichment analysis of Fig 1C, 3B and table S1. In the HPRD database, SFK substrates are a subset of the SFK PPI set.
The human-specific phosphopeptides come from the exogenous expression of Lyn and Hck.