Experimental Methods

FLAG-GFP-Paxillin phosphorylation site summary


Peptides - pax_imac_inhib.aln

                                                                                                               
PAXI_CHICK mdykddddkgpkgtvskGEELFTGVVPILVELDGDVNGHKfsvsgegegdatygkltlkficttgklpvpwptlvttltygvqcfsrYPDHMKQHDFFKS
All Expts                                                                                                      
IMAC_INHIB                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         

                                                                                                               
PAXI_CHICK AMPEGYVQERTIFFKddgnyktraevkFEGDTLVNRielkGIDFKEDGNILGHKleynynshnvyimadkqkngikvnfkirHNIEDGSVQLADHYQQNT
All Expts                                                                                                      
IMAC_INHIB                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       

                                                               1       10        20        30        40        
PAXI_CHICK PIGDGPVLLPDNHYLSTQSALSKdpnekrDHMVLLEFVTAAGITLGMDELYKMDDLDALLADLESTTSHISKRPVFLTEETPYSYPTGNHTYQEIAVPPP
All Expts                                                                                    *                 
IMAC_INHIB                                                                                   *                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
                                                                                   RPVFLTEETPYSYPTGN                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

           50        60        70        80        90       100       110       120       130       140        
PAXI_CHICK VPPPPSSEALNGTVIDPLDQWQPSVSRYGHQQPQSQSPIYSSSAKSSSASVPRDGLSSPSPRASEEEHVYSFPNKQKSAEPSPTMTSTSLGSNLSELDRL
All Expts                                    * *  **    []] *       * *   *     **      *   *      *           
IMAC_INHIB                                   * *  **    []] *       * *   *     **      *   *      *                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
                                                        SSSASVPRDGLSSPSPR               SAEPSPTMTSTSLGSNLSELDR                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
                                      YGHQQPQSQSPIYSSSAK                 ASEEEHVYSFPNKQK                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         

          150       160       170       180       190       200       210       220       230       240        
PAXI_CHICK LLELNAVQHNPPSGFSADEVSRSPSLPNVTGPHYVIPESSSSAGGKaapptkekpkrnggrGIEDVRPSVESLLDELESSVPSPVPAITVSQGEVSSPQR
All Expts                 *      * *        *    [  ]                                    []  *       *     *   
IMAC_INHIB                       * *        *    [  ]                                    []  *       *     *                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
                                                                        GIEDVRPSVESLLDELESSVPSPVPAITVSQGEVSSPQR                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
                                 SPSLPNVTGPHYVIPESSSSAGGK                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            

          250       260       270       280       290       300       310       320       330       340        
PAXI_CHICK VNASQQQTRISASSATRELDELMASLSDFKFMAQGKAGGSSSPPSTTPKPGSQLDTMLGSLQSDLNKLGVATVAKGVCGACKKPIAGQVVTAMGKTWHPE
All Expts            *                              *                                                          
IMAC_INHIB           *                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
                    ISASSATR                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         

          350       360       370       380       390       400       410       420       430       440        
PAXI_CHICK HFVCTHCQEEIGSRNFFERDGQPYCEKDYHNLFSPRCYYCNGPILDKVVTALDRTWHPEHFFCAQCGVFFGPEGFHEKdgkaycrKDYFDMFAPKcggca
All Expts                                   *                                                                  
IMAC_INHIB                                  *                                                                                                                                                                                                                                                                                                                                                                                                            
                                      DYHNLFSPR                                                                                                                                                                                                                                                                                                                                                                                                          
                                                                                                                                                                                                                                                                                                                                                                                                                                                         

          450       460       470       480       490       500       510       520       530       540        
PAXI_CHICK rAILENYISALNTLWHPECFVCRecftpfingsffehdgqpycevhyherRGSLCSGCQKPITGRcitamgkKFHPEHFVCAFCLKqlnkGTFKEQNDKP
All Expts                                                      *                                               
IMAC_INHIB                                                     *                                                                                                                                                                                                                                                                                                                                                                                                                       
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
                                                             RGSLCSGCQKPITGR                                                                                                                                                                                                                                                                                                                                                                                                           

          550         
PAXI_CHICK YCQNCFLKlfc
All Expts             
IMAC_INHIB                                          
                                                    
                                                    


Legend
*Phosphorylated sites are denoted by an asterisk below the amino acid residue.
[ ] The specific phosphorylated amino acid between the brackets can not be distinguished by the MS/MS spectra.
All Expts A summary of all phosphorylation sites detected on this molecule from all experiments.
C18_INHIB, C18,
IMAC_INHIB, IMAC
Analysis type.
Alternating, aligned peptides represent protein coverage for this experiment
Lower case amino acids have yet to be detected in any enzymatic digest analyzed by mass spectrometry.


FLAG-GFP-Paxillin (IMAC, + inhibs)

1.5-2e7 HEK cells were transiently transfected with 10 ng FLAG-GFP-Paxillin DNA and 4 ug pBS (empty vector). 1 mM peroxovandate and 10 nM Calyculin A pretreatment of cells was for 30 min prior to lysis. Extraction was for 30 min at 4degC in 25mM Tris, 100 mM NaCl, 0.5% NP-40, 1 mM peroxovanadate, 10 nM Calyculin A. Pre-cleared once with 30 uL non-specific IgG agarose for 1 hr at 4degC. Repeated preclear overnight. Immunoprecipitation (IP) was with 100 uL anti-FLAG IgG agarose beads slurry for 1.5 hr at 4degC. Washed IP 2x with 200 uL 25mM Tris, 100 mM NaCl, pH 7.4 10 min each. 10-15% of the IP was used to visualize purity by silver-stained gel. On-beads digestion of 40% of the IP was with 100 mM ammonium bicarbonate pH 8 and 500 ng trypsin. An aliquot of the digest corresponding to 38% of the original immunoprecipitated paxillin was converted to (d0) methyl esters. Combined with equal amount FLAG-GFP-Paxillin -inhibs (previously converted to d3 methyl esters) for simultaneous enrichment of phosphopeptides by IMAC followed by reverse phase separation of peptides over a 1 hr gradient coupled with online detection of phosphopeptides by ESI tandem mass spectrometry (Thermo Electron, LTQ-FTMS).