1. SHC1_p66_p52*
2. EGFR family*

Identifiers
NAME:EGFR family*:SHC1_p66_p52*

Maps_Modules
HMC:ACTIVATING_INVASION_AND_METASTASIS
 EMT Senescence   / EMT_REGULATORS 

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
Phosphorylation of SCH1 at tyrosine forms docking sitess for GRB2 adaptator protein via ist SH2 domain
The SH3 domain of GRB2 then binds to the proline-rich motifs in SOS, which is the GTP exchange factor for RAS
Via this process that SOS is recruited to the membrane and colocalizes with Ras.
Upon ligand (EGF, TGFA) binding, or upon transactiviation by Endothelin via HB-EGF ligand, EGFR is dimerized, then phosphorylated and thus activated by c-Src, which also phosphorylates and activates Shc1 (p66, p52).
EGFR binds to Shc (p66, p52) and both proteins bind to GRB2.
Both Shc and GRB2 bind to and thus recruit SOS to the membrane to colocalize and thus activate Ras.
Activation of Ras results in activation of ERK1_2, which is signal tranducer and activator of SP1, STAT3, STAT5, EGR1 and c-Fos transcription factors
SP1 stimulates expression of Collagen 1 (PMID:15240825).
STAT3 induces transcriptional expression of VEGFA, TIMP1 and TWIST (PMID:17909010).
EGR1 induces transcriptional expression of TIMP1.
c-Fos induces transcriptional expression of Endothelin1.
em_emtc_emtc_re1275( EMT Senescence  ):
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.

1. EGFR family*|​pho|​hm2:​SHC1_p66_p52*|​Y_pho|​S_pho@Cytosol

1. SHC1_p66_p52*|​Y_pho|​S_pho|​active@Cytosol + em_s2285 + SOS*@Cytosol + GRB2@Cytosol → EGFR family*|​pho|​hm2:​SHC1_p66_p52*|​Y_pho|​S_pho@Cytosol

1. em_emtc_emtc_s3418 → em_emtc_emtc_s3009