Friday, May 10, 2013

A WILD WILD TARGET!

While investigating why Gaucher disease would be linked to Lymphoproliferative disorders (Multiple Myeloma,CLL,AML LYMPHOMA INCLUDING THE HODGKIN , AND RARELY ALL.) and following downstream of CD 19, one stumble upon Grb2. just by the extent of its interactions, you know you cannot come-up empty targeting this wild gene.  The crux of the endeavor will be how to electively hit the cancer cell exclusively.

"
Grb2 is best known for its ability to link the epidermal growth factor receptor tyrosine kinase to the activation of Ras and its downstream kinases, ERK1,2. Grb2 is composed of an SH2 domain flanked on each side by an SH3 domain. Grb2 has two closely related proteins with similar domain organizations, Gads and Grap. Gads and Grap are expressed specifically in hematopoietic cells and function in the coordination of tyrosine kinase mediated signal transduction."wikipedia

Interactions

Grb2 has been shown to interact with Arachidonate 5-lipoxygenase,[5][6] Lymphocyte cytosolic protein 2,[7][8][9][10][11] GAB2,[12][13][14] B-cell linker,[15][16][17][18] Abl gene,[19][20] CD28,[21][22] FRS2,[23][24][25][26] Mitogen-activated protein kinase 9,[27][28] CD22,[29][30] NEU3,[31] ETV6,[12] MAP2,[32][33] Dock180,[34][35] PIK3R1,[36][37] SH2B1,[38][39] CRK,[40][41][42] GAB1,[7][43][44] MST1R,[45][46] DNM1,[47][48] Huntingtin,[49] Src,[50][51] Beta-2 adrenergic receptor,[52] VAV2,[53][54] ADAM15,[55] RAPGEF1,[56][57] VAV1,[58][59][60][61] HER2/neu,[54][62][63] Epidermal growth factor receptor,[2][43][53][62][64][65][66][67][68][69] PDGFRB,[69][70][71] PTK2,[72][73][74][75][76] Erythropoietin receptor,[77][78] Linker of activated T cells,[79][80][81] Dystroglycan,[82] SH3KBP1,[83][84] Granulocyte colony-stimulating factor receptor,[85] DCTN1,[86] CDKN1B,[87] Colony stimulating factor 1 receptor,[88] EPH receptor A2,[89] KHDRBS1,[43][90][91] RET proto-oncogene,[92][93] PLCG1,[94][95][96] TrkA,[97][98] PRKAR1A,[66] Janus kinase 2,[99][100] MUC1,[101] CD117,[78][102][103] Fas ligand,[104][105] Janus kinase 1,[100][106] VAV3,[53][107] BCAR1,[73][108] PTPN1,[109][110] INPP5D,[111] ITK,[112][113] SHC1,[51][53][114][115][116][117][118][119][120][121][122][123][124][125][126][127][128][129][130][131][132] PTPN12,[133] C-Met,[134][135] PTPN11,[71][85][127][136][137][138][139][140][141] Glycoprotein 130,[61] PTPN6,[51][136][142] Syk,[51][136] MAP4K1,[143][144][145][146] Wiskott-Aldrich syndrome protein,[147][148] NCKIPSD,[149][150] PTPRA,[151][152][153] BCR gene,[12][115][154][155][156][157] CBLB,[158][159][160] Cbl gene,[9][24][51][90][124][158][161][162][163][164][165][166][167] SOS1,[8][24][42][43][48][51][53][60][68][90][95][101][115][122][124][131][168][169][170][171][172] IRS1,[100][114][173] TNK2,[116][174] MED28,[175] MAP3K1[176] and HNRNPC.[177]


You just look at the variety of interaction and you know this is an important step to anything in the cellular sun!  WOW!
Gerb2 a lifetime project!
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