p-Y546,Y584-PTPN11 (in CSF3 dimer:2xp-4Y-CSF3R:LYN:p-Y-JAK1:p-JAK2:p-SYK:p-HCK:p-TYK2:SHC:GRB2:PTPN11) dephosphorylates KRAS

Stable Identifier
R-HSA-9674816
Type
Reaction [transition]
Species
Homo sapiens
Compartment
plasma membrane
ReviewStatus
5/5
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p-Y546,Y584-PTPN11 (in CSF3 dimer:2xp-4Y-CSF3R:LYN:p-Y-JAK1:p-JAK2:p-SYK:p-HCK:p-TYK2:SHC:GRB2:PTPN11) dephosphorylates KRAS
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CSF3 (G-CSF) signaling activates ERKs (ERK1, ERK2) via RAS. One possible mechanism of RAS activation is the dephosphorylation of KRAS (the dominant isoform of RAS in hematopoietic cells) by phosphorylated PTPN11 (also known as SHP-2 or SHP2) (Kano et al. 2019, also inferred from dephosphorylation of the HRAS paralog in Bunda et al. 2015) bound to phosphorylated CSF3R. Dephosphorylation of RAS increases the association of RAS with its downstream effector RAF. Inhibition of PTPN11 in mouse cells indicates that this pathway accounts for most but not all activation of ERKs in response to CSF3 (Jack et al. 2009, Zhang and Friedman 2011). Guanyl nucleotide exchange factors SOS or VAV bound to GRB2 may also be responsible for some activation of RAS in response to CSF3, but this has not yet been demonstrated.
Literature References
PubMed ID Title Journal Year
30644389 Tyrosyl phosphorylation of KRAS stalls GTPase cycle via alteration of switch I and II conformation

Kano, Y, Gebregiworgis, T, Marshall, CB, Radulovich, N, Poon, BPK, St-Germain, J, Cook, JD, Valencia-Sama, I, Grant, BMM, Herrera, SG, Miao, J, Raught, B, Irwin, MS, Lee, JE, Yeh, JJ, Zhang, ZY, Tsao, MS, Ikura, M, Ohh, M

Nat Commun 2019
Participants
Input
Output
Participates
as an event of
Catalyst Activity

protein tyrosine phosphatase activity of CSF3 dimer:2xp-4Y-CSF3R:LYN:p-Y-JAK1:p-JAK2:p-SYK:p-HCK:p-TYK2:p-Y-SHC1:GRB2:p-Y643-GAB2:p-Y546,Y584-PTPN11 [plasma membrane]

Physical Entity
CSF3 dimer:2xp-4Y-CSF3R:LYN:p-Y-JAK1:p-JAK2:p-SYK:p-HCK:p-TYK2:p-Y-SHC1:GRB2:p-Y643-GAB2:p-Y546,Y584-PTPN11 [plasma membrane] (Homo sapiens)
Activity
protein tyrosine phosphatase activity (GO:0004725)
Orthologous Events
p-Y546,Y584-PTPN11 (in CSF3 dimer:2xp-4Y-CSF3R:LYN:p-Y-JAK1:p-JAK2:p-SYK:p-HCK:p-TYK2:SHC:GRB2:PTPN11) dephosphorylates KRAS (Bos taurus)
p-Y546,Y584-PTPN11 (in CSF3 dimer:2xp-4Y-CSF3R:LYN:p-Y-JAK1:p-JAK2:p-SYK:p-HCK:p-TYK2:SHC:GRB2:PTPN11) dephosphorylates KRAS (Canis familiaris)
p-Y546,Y584-PTPN11 (in CSF3 dimer:2xp-4Y-CSF3R:LYN:p-Y-JAK1:p-JAK2:p-SYK:p-HCK:p-TYK2:SHC:GRB2:PTPN11) dephosphorylates KRAS (Mus musculus)
p-Y546,Y584-PTPN11 (in CSF3 dimer:2xp-4Y-CSF3R:LYN:p-Y-JAK1:p-JAK2:p-SYK:p-HCK:p-TYK2:SHC:GRB2:PTPN11) dephosphorylates KRAS (Rattus norvegicus)
p-Y546,Y584-PTPN11 (in CSF3 dimer:2xp-4Y-CSF3R:LYN:p-Y-JAK1:p-JAK2:p-SYK:p-HCK:p-TYK2:SHC:GRB2:PTPN11) dephosphorylates KRAS (Sus scrofa)
Authored
May, B  (2020-01-15)
Reviewed
Touw, IP  (2020-12-12)
Created
May, B  (2020-01-27)
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