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. Author manuscript; available in PMC: 2016 Jun 15.
Published in final edited form as: Bioorg Med Chem. 2015 Apr 4;23(12):2786–2797. doi: 10.1016/j.bmc.2015.03.075

Figure 4. Putative functions of SHP1 and SHP2 in platelets and megakaryocytes.

Figure 4

Figure 4

Figure 4

Figure 4

(A/B) SHP1 and SHP2 have been implicated in regulating proximal signaling events downstream of the immunoreceptor tyrosine-based activation motif (ITAM)-containing collagen receptor complex GPVI-FcRγ, and the hemi-ITAM-containing podoplanin receptor CLEC-2. (C) SHP2 has also been implicated as a negative regulator of the integrin αIIbβ3 in mice. It should be noted that the ITAM-containing low affinity immunoglobulin receptor FcγRIIA acts as a docking site for Syk downsream of αIIbβ3 in human platelets, but not in mouse platelets, which do not express FcγRIIA. (D) The best-characterized function of SHP2 in the megakaryocyte lineage is its positive regulatory role of the Ras-ERK1/2 pathway, downstream of the thrombopoietin (Tpo) receptor MPL. However, the exact mechanism remains ambiguous. Functions illustrated in this figure are mainly based on findings from SHP1 and SHP2 conditional knockout mice and need to be validated in mouse and human platelets through the use of SHP1- and SHP2-specific inhibitors.