GRB2

Protein GRB2 map

Identifiers
growth factor receptor-bound protein 2
HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 GENECARDS:GRB2 REACTOME:404631 KEGG:2885 ATLASONC:GRB2ID386ch17q25 WIKI:GRB2

Maps_Modules
 EMT  map  / EMT_REGULATORS  map
 Survival  map  / MAPK  map
 Survival  map  / PI3K_AKT_MTOR  map

References
PMID:17673906
SHC1 gene has 3 corresponding protein isoforms: p66, p52 and p46
Upon TGFB stimulation, the activated TGFBR1 recruits and directly phosphorylates SHC1 (p66 or p52) on tyrosine and serine.
TGFB-induced SHC1 phosphorylation induces SHC1 (p66 or p52) association with Grb2 and Sos
GRB2 is an adaptator for Ras
Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK.
PMID:17496910
PMID:15574420
PMID:11777939

GRB2@Cytoplasm

References
e_re1275( EMT  map ):
In general, growth factor stimulation leads to the activation of receptor tyrosine kinases and to the phosphorylation of the receptor tail.
The resultant phosphotyrosines form docking sites for adaptator proteins (e.g. GRB2 via its SH2 domain).
The SH3 domain of adaptator (e.g. GRB2) then binds to the proline-rich motifs in the GTP exchange factor (i.e. GEF) for RAS (e.g. SOS)
Via this process that GEF (e.g. SOS) is recruited to the membrane where it colocalizes with and activates Ras.
PMID:17673906
SHC1 gene has 3 corresponding protein isoforms: p66, p52 and p46
Upon TGFB stimulation, the activated TGFBR1 recruits and directly phosphorylates SHC1 (p66 or p52) on tyrosine and serine.
TGFB-induced SHC1 phosphorylation induces SHC1 (p66 or p52) association with Grb2 and Sos


Modifications:
In compartment: Cytoplasm
  1. GRB2@Cytoplasm map

Participates in complexes:
In compartment: Cytoplasm

  1. FGFR family*:​FRS2|​pho:​GRB2:​SOS*@Cytoplasm map

  2. EGFR family*|​pho|​hm2:​GRB2:​SHC1_p66_p52*|​Y_pho|​S_pho:​SOS*@Cytoplasm map

In compartment: Endosome

  1. GAB1:​GF:​GRB2:​PI3,4,5-P3:​RAS*:​RTK*|​pho|​pho|​hm2:​SOS*:​p110*:​p85*@Endosome map

In compartment: Late Endosomes

  1. GRB2:​LAMTOR2:​MEK*:​MP1*:​RAS*|​pho:​RTK*:​SOS*@Late Endosomes map

  2. GRB2:​LAMTOR2:​MEK*|​pho|​pho:​MP1*:​RAF1|​pho:​RAS*|​pho:​RTK*:​SOS*@Late Endosomes map
  3. ERK*|​pho|​pho:​GRB2:​LAMTOR2:​MEK*|​pho|​pho:​MP1*:​RAF1|​pho:​RAS*|​pho:​RTK*:​SOS*@Late Endosomes map

In compartment: Lipid Raft

  1. GAB1|​Y977_pho|​Y989_pho:​GF:​GRB2:​PI3,4,5-P3:​RAS*:​RTK*|​pho|​pho|​hm2:​SOS*:​p110*:​p85*@Lipid Raft map

In compartment: Plasma Membrane

  1. GRB2:​RTK*:​SOS*@Plasma Membrane map

  2. GRB2:​RAC1|​pho:​RTK*:​SOS*@Plasma Membrane map
  3. GRB2:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map
  4. BRAF|​pho:​GRB2:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map
  5. GRB2:​RAF1|​pho:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map
  6. BRAF|​pho:​GRB2:​KSR1-NTER*:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map
  7. BRAF|​pho:​GRB2:​KSR1:​MEK*|​pho|​pho:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map
  8. BRAF|​pho:​ERK*|​pho|​pho:​GRB2:​KSR1:​MEK*|​pho|​pho:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map

Participates in reactions:
As Reactant or Product:

  1. SHC1_p66_p52*|​Y_pho|​S_pho|​active@Cytoplasm map + EGF family*:​EGFR family*|​pho|​hm2@Cytoplasm map + SOS*@Cytoplasm map + GRB2@Cytoplasm map map EGFR family*|​pho|​hm2:​GRB2:​SHC1_p66_p52*|​Y_pho|​S_pho:​SOS*@Cytoplasm map

  2. FRS2|​pho|​active@Cytoplasm map + FGF family*|​hm2:​FGFR family*:​Heparin|​hm2@Cytoplasm map + GRB2@Cytoplasm map + SOS*@Cytoplasm map + PTPN11|​pho|​active@Cytoplasm map map FGFR family*:​FRS2|​pho:​GRB2:​SOS*@Cytoplasm map
  3. p110*:​p85*@Cytoplasm map + s_s_akt1_s53 + PI3,4,5-P3@Lipid Raft map + RTK*@Cytoplasm map + GF@default map + RAS*@Cytoplasm map + GAB1|​Y977_pho|​Y989_pho@Cytoplasm map map GAB1|​Y977_pho|​Y989_pho:​GF:​GRB2:​PI3,4,5-P3:​RAS*:​RTK*|​pho|​pho|​hm2:​SOS*:​p110*:​p85*@Lipid Raft map
  4. GAB1:​GF:​GRB2:​PI3,4,5-P3:​RAS*:​RTK*|​pho|​pho|​hm2:​SOS*:​p110*:​p85*@Endosome map map Ubiquitination@Cytoplasm map
  5. GAB1|​Y977_pho|​Y989_pho:​GF:​GRB2:​PI3,4,5-P3:​RAS*:​RTK*|​pho|​pho|​hm2:​SOS*:​p110*:​p85*@Lipid Raft map map GAB1:​GF:​GRB2:​PI3,4,5-P3:​RAS*:​RTK*|​pho|​pho|​hm2:​SOS*:​p110*:​p85*@Endosome map
  6. RAF1@Cytoplasm map + GRB2:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map map GRB2:​RAF1|​pho:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map
  7. GRB2:​RAF1|​pho:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map map GRB2:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map + RAF1|​pho@Mitochondria map
  8. GRB2:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map + BRAF@Cytoplasm map map BRAF|​pho:​GRB2:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map
  9. GRB2:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map + MAP3K1@Cytoplasm map map MAP3K1|​pho:​RAS*|​pho:​RTK*@Cytoplasm map
  10. GRB2:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map + MAP3K2_3*@Cytoplasm map map MAP3K2_3*|​pho:​RAS*|​pho:​RTK*@Cytoplasm map
  11. GRB2:​RTK*:​SOS*@Plasma Membrane map + RAC1@Plasma Membrane map map GRB2:​RAC1|​pho:​RTK*:​SOS*@Plasma Membrane map
  12. BRAF|​pho:​GRB2:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map + KSR1:​MEK*@Cytoplasm map map BRAF|​pho:​GRB2:​KSR1:​MEK*|​pho|​pho:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map
  13. GRB2:​RAC1|​pho:​RTK*:​SOS*@Plasma Membrane map map RAC1@Plasma Membrane map + GRB2:​RTK*:​SOS*@Plasma Membrane map
  14. GRB2:​RAC1|​pho:​RTK*:​SOS*@Plasma Membrane map + MAP3K10_11*@Cytoplasm map map MAP3K10_11*|​pho:​RAC1|​pho:​RTK*@Cytoplasm map
  15. BRAF|​pho:​GRB2:​KSR1:​MEK*|​pho|​pho:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map + ERK*@Cytoplasm map map BRAF|​pho:​ERK*|​pho|​pho:​GRB2:​KSR1:​MEK*|​pho|​pho:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map
  16. GRB2:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map + LAMTOR2:​MEK*:​MP1*@Late Endosomes map map GRB2:​LAMTOR2:​MEK*:​MP1*:​RAS*|​pho:​RTK*:​SOS*@Late Endosomes map
  17. ERK*|​pho|​pho:​GRB2:​LAMTOR2:​MEK*|​pho|​pho:​MP1*:​RAF1|​pho:​RAS*|​pho:​RTK*:​SOS*@Late Endosomes map map GRB2:​LAMTOR2:​MEK*:​MP1*:​RAS*|​pho:​RTK*:​SOS*@Late Endosomes map + ERK*@Cytoplasm map + RAF1@Cytoplasm map
  18. RAF1@Cytoplasm map + GRB2:​LAMTOR2:​MEK*:​MP1*:​RAS*|​pho:​RTK*:​SOS*@Late Endosomes map map GRB2:​LAMTOR2:​MEK*|​pho|​pho:​MP1*:​RAF1|​pho:​RAS*|​pho:​RTK*:​SOS*@Late Endosomes map
  19. ERK*@Cytoplasm map + GRB2:​LAMTOR2:​MEK*|​pho|​pho:​MP1*:​RAF1|​pho:​RAS*|​pho:​RTK*:​SOS*@Late Endosomes map map ERK*|​pho|​pho:​GRB2:​LAMTOR2:​MEK*|​pho|​pho:​MP1*:​RAF1|​pho:​RAS*|​pho:​RTK*:​SOS*@Late Endosomes map
  20. s_s_mpk1_s1009 + RTK*@Plasma Membrane map map GRB2:​RTK*:​SOS*@Plasma Membrane map
  21. GRB2@Cytoplasm map + SOS*@Cytoplasm map map s_s_mpk1_s1009
  22. GRB2@Cytoplasm map + GAB1@Cytoplasm map map s_s_mpk1_s1010
  23. BRAF|​pho:​ERK*|​pho|​pho:​GRB2:​KSR1:​MEK*|​pho|​pho:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map map KSR1:​MEK*@Cytoplasm map + BRAF|​pho:​GRB2:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map + ERK*|​pho|​pho@Cytoplasm map
  24. BRAF|​pho:​GRB2:​KSR1:​MEK*|​pho|​pho:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map map BRAF|​pho:​GRB2:​KSR1-NTER*:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map + KSR1-CTER*:​MEK*@Cytoplasm map
  25. ERK*|​pho|​pho:​GRB2:​LAMTOR2:​MEK*|​pho|​pho:​MP1*:​RAF1|​pho:​RAS*|​pho:​RTK*:​SOS*@Late Endosomes map map GRB2:​LAMTOR2:​MEK*|​pho|​pho:​MP1*:​RAF1|​pho:​RAS*|​pho:​RTK*:​SOS*@Late Endosomes map + ERK*|​pho|​pho@Cytoplasm map
  26. GRB2:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map map RAS*@Plasma Membrane map + GRB2:​RTK*:​SOS*@Plasma Membrane map
  27. BRAF|​pho:​ERK*|​pho|​pho:​GRB2:​KSR1:​MEK*|​pho|​pho:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map map ERK*|​pho|​pho:​KSR1:​MEK*|​pho|​pho@Cytoplasm map + BRAF|​pho:​GRB2:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map
  28. RAS*@Plasma Membrane map + GRB2:​RTK*:​SOS*@Plasma Membrane map map GRB2:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map

As Catalyser:

  1. GDP:​HRAS@Cytoplasm map map GTP:​HRAS@Cytoplasm map

  2. PtdIns(4,5)-P2@Lipid Raft map map PI3,4,5-P3@Lipid Raft map
  3. FRS2@Plasma Membrane map map FRS2|​pho@Plasma Membrane map
  4. IMP*:​KSR1:​MEK*@Cytoplasm map map IMP*@Cytoplasm map + KSR1:​MEK*@Cytoplasm map

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