e_re382( EMT ):
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.
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
e_re385( EMT ):
Activated HRAS (GTP bound forn) is associated with the plasma membrane.
Inactive RAF1 is associated in the cytoplasm with YWHAB via S259 phosphorylation site and also binding site.
RAF1 has a RAS-binding Cysteine-rich domain (CRD) and an additional RAS-binding domain (RBD).
RAF1 binds activated HRAS via the RBD. This binding displaces YWHAB from Ser259 and unmasks the CRD.
e_re835( EMT ):
Cross-talk between small GTPase signaling pathways.
HRAS activates TIAM1 which is a GEF for Rac1.
RalBP1 (which is an effector for RalA and RalB) inactivates Rac1
Participates in complexes:
In compartment: Cytoplasm
Participates in reactions:
As Reactant or Product:
- GDP:HRAS@Cytoplasm → GTP:HRAS@Cytoplasm
- RAF1|S259_pho|S621_pho|S_pho|closed:YWHAB@Cytoplasm + GTP:HRAS@Cytoplasm → GTP:HRAS:RAF1|S259_pho|S621_pho|S_pho|closed@Cytoplasm + YWHAB@Cytoplasm
- GTP:HRAS@Cytoplasm → GDP:HRAS@Cytoplasm