Skip to main content

Table 1 Literature confirmed interactions 39 array-positive interactions were experimentally verified or confirm previously reported interactions while 23 array-negative interactions empirically suggest a threshold corresponding to a K D of approximately 5 to 10 μM for this data set

From: SRC Homology 2 Domain Binding Sites in Insulin, IGF-1 and FGF receptor mediated signaling networks reveal an extensive potential interactome

Peptide sequence

Protein/position

Expected partner

Array positive

Affinity (KD)/relative affinity (IC50)

References

Comments and other SH2 domains bound

ATDDpYAVPPPR

p62DOK1 (Y409), similar to p130Cas (Y410)

Crk

Yes

N.A.

[87]

Crkl, Hck

EDDGpYDVPKPP

Cbl (Y774)

Crk

Yes

N.A.

[88]

Crkl

  

Hck

Yes

N.A.

[89, 90]

Fgr, Src, Yes

AEDVpYDVPPPA

p130Cas (Y362)

Crk

Yes

KD = 0.545 μM

[87]

Src, Hck, Fyn

GLDEpYDEVPMP

B3AT (Y921)*

Nck1

Yes

KD = 0.06 μM

[91]

*Similar to the TIR10 peptide (EHIpYDEVAAD). Fer

DDPSpYVNVQNL

ShcA (Y426)

Grb2

Yes

KD = 23nM

[92, 93]

Gads, Grap

  

Grb2

Yes

KD = 53 ± 8nM

[94]

 

ADNDpYIIPLPD

PDGFRb (Y1021)

Plcγ-N

Yes

KD = 0.65 - 2.2nM1

[95]

1Tandem SH2 domains of PLCG1 were tested against a tandem phospho-peptide of PDGFRβ Y1009/Y1021.

  

Plcγ-C

Yes

KD = 0.65 - 2.2nM1

[95–97];

Brk

  

Plcγ-C

Yes

KD = 4.1 ± 0.8 μM

[98]

 
  

Vav1

Yes

N.A.

[99]

 
  

PI3K_N

No

ID50 = 45 ± 14 μM

[79]

Below Threshold

SLTIpYAQVQKA

SLAM (Y280)

Sh2d1b

Yes

KD = 131nM

[100]

 

HDGLpYQGLSTA

CD150 (Y142)

Shc1

No

KD = 50 μM

[101]

Below Threshold

STVEpYSTVVHS

gp130/IL-6 Receptor (Y759)

Ptpn11

No

N.A.

[102]

PTPN11_N is 1.33X Mean, PTPN11_C is 2.8X Mean Brdg1, Brk, Sh2d1b

AEPQpYEEIPIY

Middle T-antigen (Y323)

Src

Yes

KD = 0.55-0.8 μM

[19]

Blk, Brk, Fer, Fgr, Hck, Lyn, Nck1, Shc1, Yes

  

Lck

Yes

KD = 1.3 ± 0.2 μM

[103]

 

SDDDpYDDVDIP

HPK1 (Y379)

Nck1

Yes

N.A.

[104]

Fer, SLNK (similar to BLNK and SLP76)

TRDIpYETDpYpYR

InsR (Y1185,89,90)

Plcγ_C

Yes

N.A.

[105]

Crk, Crkl, Fer, Grb7, PI3K1_C

EDLSpYGDVPPG

IRS-1 (Y151)

Nck1

No

N.A.

[106]

1.76X Mean Abl1, Blk, Fyn, Lck, Lyn, Sh2d1b, Shc1, Ship2, Slnk, Yes

ELSNpYICMGGK

IRS-1 (Y465)

Ptpn11_N

No

IC50 = 48 ± 16 μM

[107]

Below Threshold, 0.9X Mean

SIEEpYTEMMPA

IRS-1 (Y551)

Ptpn11_N

No

IC50 = 11 ± 1.0 μM

[107]

Below Threshold, 0.56X Mean

GSGDpYMPMSPK2

IRS-1 (Y612)

PI3K1_N

No

ID50 = 0.7-1.1 μM

[79]

2Peptide Y632 (GSGDpYMPMSPK) on IRS-1 is similar to Y612 (TDDGpYMPMSPG) on IRS-1.

DPNGpYMMMSPS

IRS-1 (Y662)

Ptpn11_N

No

IC50 = 96 ± 13 μM

[107]

Below Threshold, 0.54X Mean

SPGEpYVNIEFG

IRS-1 (Y896)

Ptpn11_N

Yes

IC50 = 4.8 ± 1.0 μM

[107, 108]

Abl2, Blk, Dapp1, Grb7, Itk, Mist, PI3K1_N, PI3K1_C, PTPN11_N, PLCγ_C, Rasa1_N, Rasa1_C, Sh2b, Sh2d1b, Shb, Shf, Shd, She, Syk_C, Vav1, Yes

  

Grb2

Yes

KD = 35nM

[92, 108, 109]

Gads, Grap

APVSpYADMRTG

IRS-1 (Y1012)

Ptpn11_N

No

KD = 110 ± 23 μM

[107]

Below Threshold, 0.59X Mean

NGLNpYIDLDLV

IRS-1 (Y1179)

Ptpn11_N

Yes3

KD = 3.0 ± 0.60nM

[95, 108, 110]

3Tandem SH2 domains of PTPN11 was used to bind to the tandem motif of IRS-1

  

Ptpn11_N

Yes

IC50 = 1.1 ± 0.5 μM

[107]

Abl1, Ptpn11_N, Plcγ_C, Rasa1_N, Shb, Shf, Shd, She, Yes

  

Fyn

No

N.A.

[46]

0.45X Mean

DLSApYASISFQ

IRS-1 (Y1229)

Ptpn11_N

No

IC50 = 25 ± 4.2 μM

[107]

Below Threshold, 2.78X Mean

  

Ptpn11_C

No

N.A.

[108]

1.59X Mean

  

Fyn

No

N.A.

[46]

0.48X Mean

GGEFpYGYMTMD

IRS-2 (Y540)

Plcγ_C

Yes

N.A.

[111]

Dapp1, Grb7

PNGDpYLNVSPS

IRS-2 (Y766)

Grb2

Yes

N.A.

[112]

Sh2d1b, Vav1

SNQEpYLDLSMP

FGFR1 (Y766)

Shb

No

N.A.

[113]

Similar peptide to Y760 of FGFR3 but has weak binding, 0.45X Mean

  

Plcγ

No

N.A.

[55]

PLCγ_N – 0.52X Mean

      

PLCγ_C – 0.21X Mean

THDLYMIMREA

FGFR3 (Y724)

Sh2b

No

N.A.

[114]

0.44X Mean

STDEpYLDLSAP

FGFR3 (Y760)

Sh2b

No

N.A.

[114]

0.46X Mean

VSEEYLDLRLT

FGFR4 (754)

Plcγ

No

N.A.

[115]

SHD

QVHTpYVNTTGV

FRS2 (Y196)

Grb2

Yes

N.A.

[116]

Abl2, Gads, Grap, PI3K1_C

NKLVpYENINGL

FRS2 (Y306)

Grb2

Yes

N.A.

[116]

Grap, Grb7, Sh2d2a

ALLNpYENLPSL

FRS2 (Y349)

Grb2

Yes

N.A.

[116]

Abl1, Abl2, Gads, Grap, Grb2, Grb7, PI3K1_C, Sh2d2a, Sh3bp2

PMHNpYVNTENV

FRS2 (Y392)

Grb2

Yes

N.A.

[116]

Gads, Grap

RQLNpYIQVDLE

FRS2 (Y436)

Ptpn11_N

Yes

N.A.

[117]

Itk, Mist, PLCγ_C, Rasa1_N, Shb, Shd, She, Syk_C

NPGFpYVEANPM

PLCγ1 (Y783)

Plcγ_C

No

N.A.

[118]

PLCγ_C at 1.03X mean; Zap70_N

EQDEYDIPRHL

p130Cas (Y234)

Crk

Yes

N.A.

[87]

Brk, Crkl, Fyn, Lck, Lyn, Shc1, Yes

PQDIYDVPPVR

P130Cas (Y249)

Crk

Yes

N.A.

[87]

Crkl, Zap70_N

WMEDpYDYVHLQ

p130Cas (Y664)

Nck1

Yes

N.A.

[87, 119]

Bcar3, Brk, Crk, Crkl, Dapp1, Fer, Grb7, Matk, PI3K1_N, Rasa1_N, Rasa1_C, Sh3bp2

  

Bmx

Yes

N.A.

[120]

Itk

  

Src

No

KD = 25-46nM

[119, 121]

2.45X mean

  

Lck

No

N.A.

[121]

2.03X mean

PPALpYAEPLDS

p62DOK1 (Y296)

Rasa1_N

Yes

N.A.

[122]

Abl1, Nck1, Vav1, Zap70_N

  

Rasa1_C

Yes

N.A.

[122]

 

QDSLpYSDPLDS

p62DOK1 (Y315)

Rasa1_C

Yes

N.A.

[122]

Abl1, Blk, Crk, Lck, Lyn, Nck1, Src, Zap70_N

EDPIpYDEPEGL

p62DOK1 (Y362)

Nck1

Yes

N.A.

[123]

Blk, Hck, Lck, Lyn, Shc1, Src

  

Abl1

Yes

N.A.

[124]

 

KEEGpYELPYNP

p62DOK1 (Y398)

Rasa1_C

Yes

N.A.

[123]

Abl1, Blk, Brk, Fgr, Fyn, Hck, Lck, Lyn, Nck1, Sh2d1b, Shc1, Ship2, Src, Vav1, Yes

  

Rasa1_N

Yes

N.A.

[123]

 
  1. A set of control peptides with previously reported SH2 domain targets was included on each array. We further identified a set of literature-reported interactions between specific peptides present on the arrays and SH2 domains used in this study. Peptide sequence is indicated along with the source protein and corresponding position of the relevant phosphotyrosine residue. SH2 domains that were expected to bind to each peptide are noted along with the observed array-positive status. Measured equilibrium dissociation values (KD) or relative affinity (IC50) values reported in the literature are noted. Additional array-positive SH2 domains identified as interacting with each peptide are also indicated along with explanatory comments
  2. N.A. – No Affinity Determined, # - IC50 Relative Affinities.