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Table 1 A meta-map of Gab2 phosphorylation

From: Alterations of Gab2 signalling complexes in imatinib and dasatinib treated chronic myeloid leukaemia cells

Residue

This study

IM-treated K562 cells [[38]]

EGF-stimulated MCF-10A cells [[19]]

Phospho-sitePlus

Protein docking site or other known function

Conserved in Gab1

S2

X

     

Y48

 

X

 

X

 

X

Y49

   

X

 

X

S132

X

     

S133

X

 

X

X

  

S140

X

 

X

X

  

S141

X

 

X

X

  

S146

X

     

S148

X

 

X

X

  

S149

X

 

X

X

  

S159

Western (Figure 1A)

 

X

X

Negative regulatory site; AKT substrate [21]

 

S164

  

X

X

  

T171

   

X

 

X

Y194

   

X

  

S210

X

 

X

X

14-3-3 binding and negative regulatory site [19, 23]

 

S218

X

 

X

X

 

X

S223

X

 

X

X

  

T225

X

     

Y249

   

X

CrkL/PLCγ [13]

X

S250

   

X

 

X

S264

X

 

X

X

 

X and phosphorylated [57]

T265

   

X

 

X

Y266

 

X

 

X

CrkL/PLCγ [13]

X

T278

X

 

X

   

S281

X

 

X

X

  

T283

X

     

S285

X

     

T287

X

 

X

X

  

Y293

 

X

X

X

CrkL [13]

X

T294

   

X

  

T319

X

    

X

Y324

X

   

CrkL/PLCγ [13]

X

T329

X

    

X

T331

  

X

  

X

T343

X

     

S368

X

    

X

T385

X

 

X

X

  

T391

X

 

X

X

14-3-3 binding and negative regulatory site [19, 23]

X and phosphorylated [57]

S404

X

  

X

 

X

S405

X

 

X

X

 

X

T408

   

X

  

Y409

 

X

 

X

 

X

Y411

   

X

  

S422

X

    

X and phosphorylated [57]

S425

X

     

S427

X

     

S443

X

     

S448

X

     

Y452

X

  

X

p85 recruitment site; Resilient against IM and DST in K562 cells [9]

X

S472

    

X

X

S474

    

X

X

Y476

    

X

X

S480

X

 

X

X

 

X

S488

X

  

X

 

X

Y491

X

  

X

  

S506

X

     

S543

X

 

X

X

ERK dependent phosphorylation of the S543 equivalent critical for PH-domain mediated membrane recruitment of Gab1 [56]. ERK consensus motif (PxxSP) conserved in Gab2

X

S550

   

X

  

Y563

   

X

  

Y584

   

X

p85 [13]

X

S611

   

X

  

Y614

   

X

Shp2 [13]

X

S622

X

 

X

X

 

X

S623

X

 

X

X

  

S625

X

  

X

 

X

S631

X

  

X

  

T632

   

X

  

S633

   

X

  

S634

X

     

T636

X

  

X

 

X

S637

X

  

X

  

Y643

X

  

X

Shp2 [13]

X

  1. Comparison of the phospho-maps of Gab2 from this study with those established for IM treated K562 cells [38], EGF stimulated MCF-10A cells [19] and the sites listed in the curated phosphosite database (http://www.phosphosite.org). Note that in addition to other entries, the entries from the MCF-10A cells are also represented in this database. See Wöhrle et al. (2009) for further details on the indicated docking sites. Gab2 phoshorylation sites that have a homotopic counterpart in Gab1 (incl. conserved S⇔T conversions) were identified by comparing the human Gab2 (NP_53679) and Gab1 (NP_997006.1) sequences using the BLASTP 2.2.27+ tool. However, it should be noted that in many cases only the phosphorylation site itself and not its context were conserved between both paralogues, like it was described for the T391/T387 in Gab2/Gab1 [19, 57]. All new Gab2 phosphorylation sites, identified in this study were marked in bold.