Reactome | Phosphorylated SHC1 recruits SHIP

Phosphorylated SHC1 recruits SHIP

Stable Identifier

R-HSA-913374

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol, plasma membrane

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

Immune System (Homo sapiens)

- Cytokine Signaling in Immune system (Homo sapiens)
  - Signaling by Interleukins (Homo sapiens)
    - Interleukin-2 family signaling (Homo sapiens)
      - Interleukin receptor SHC signaling (Homo sapiens)
        
        Phosphorylated SHC1 recruits SHIP (Homo sapiens)
    - Interleukin-3, Interleukin-5 and GM-CSF signaling (Homo sapiens)
      - Interleukin receptor SHC signaling (Homo sapiens)
        
        Phosphorylated SHC1 recruits SHIP (Homo sapiens)

General

SBML | | PDF

SVG | | PPTX | SBGN

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

SHIP dephosphorylates PIP3 and may limit the magnitude or duration of signaling events that are dependent upon PIP3-mediated membrane recruitment of plextrin homology (PH) domain signalling proteins such as PI3K and Akt (Aman et al. 1998). The PTB domain of SHC1 binds to phosphorylated tyrosine residues on SHIP. Mutations that inactivate the PTB domain prevent this binding and substitution of F for Y917 and Y1020 on SHIP prevents creation of the phosphotyrosine motifs that are recognized by the SHC1 PTB domain, blocking the interaction (Lamkin et al. 1997). A functional SHIP SH2 domain is also reported as a requirement for association of SHIP with Shc (Liu et al. 1997). GRB2 stabilizes the SHC1/SHIP complex (Harmer & DeFranco 1999), presumably by simultaneously binding via its SH3 domains to SHIP and via its SH2 domain to phosphotyrosines on SHC1, forming a ternary complex of SHC1:GRB2:SHIP described as inducible by IL-3, IL-5 or GM-CSF by many authors (Jucker et al. 1997, Lafrancone et al. 1995, Odai et al. 1997). SHIP2 also associates with SHC1 but does not appear to require Grb2 for stability (Wisniewskiet al. 1999).

Literature References

PubMed ID	Title	Journal	Year
9108392	Purification and molecular cloning of SH2- and SH3-containing inositol polyphosphate-5-phosphatase, which is involved in the signaling pathway of granulocyte-macrophage colony-stimulating factor, erythropoietin, and Bcr-Abl Yazaki, Y, Sasaki, K, Hirai, H, Mitani, K, Iwamatsu, A, Ueno, H, Nakamoto, T, Odai, H, Yamagata, T	Blood	1997
9099679	Shc interaction with Src homology 2 domain containing inositol phosphatase (SHIP) in vivo requires the Shc-phosphotyrosine binding domain and two specific phosphotyrosines on SHIP Walk, SF, Krystal, G, Liu, L, Ravichandran, KS, Damen, JE, Lamkin, TD	J Biol Chem	1997
10570274	Tyrosine phosphorylation of shc in response to B cell antigen receptor engagement depends on the SHIP inositol phosphatase Ingham, RJ, Dang-Lawson, M, Gold, MR, van der Geer, P, Kurosaki, T, Okada, H, Dinglasan, J	J Immunol	1999