Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus (PubMed:14967142). Positively regulates MAPK signal transduction pathway (By similarity). Dephosphorylates GAB1, ARHGAP35 and EGFR (By similarity). Dephosphorylates ROCK2 at 'Tyr-722' resulting in stimulation of its RhoA binding activity (By similarity). Dephosphorylates CDC73 (By similarity). Dephosphorylates SOX9 on tyrosine residues, leading to inactivate SOX9 and promote ossification (PubMed:29644115). H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] + phosphate Interacts with CD84 and with phosphorylated SIT1 and MZPL1. Interacts with FCRL4, FCRL6 and ANKHD1. Interacts with GAREM1 (tyrosine phosphorylated); the interaction increases MAPK/ERK activity and does not affect the GRB2/SOS complex formation (By similarity). Interacts with PTPNS1 and BCAR3. Interacts with phosphorylated LIME1. Interacts with SHB and INPP5D/SHIP1. Interacts with KIR2DL1; the interaction is enhanced by ARRB2 (By similarity). Interacts with GAB2. Interacts with TERT; the interaction retains TERT in the nucleus. Interacts with PECAM1 and FER. Interacts with EPHA2 (activated); participates in PTK2/FAK1 dephosphorylation in EPHA2 downstream signaling (By similarity). Interacts with MILR1 (tyrosine phosphorylated). Interacts with FLT1 (tyrosine-phosphorylated), FLT3 (tyrosine-phosphorylated), FLT4 (tyrosine-phosphorylated), KIT and GRB2. Interacts with ROS1; mediates PTPN11 phosphorylation. Interacts with PDGFRA (tyrosine phosphorylated). Interacts with PDGFRB (tyrosine phosphorylated); this interaction increases the PTPN11 phosphatase activity. Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated). Interacts with CEACAM1 (via cytoplasmic domain); this interaction depends on the monomer/dimer equilibrium and is phosphorylation-dependent (PubMed:19948503, PubMed:9867848). Interacts with MPIG6B (via ITIM motif) (PubMed:23112346). Interacts with SIGLEC10 (PubMed:23374343). Interacts with Lilrb4a (when tyrosine phosphorylated) (PubMed:10026201). Interacts with SIGLEC10 (By similarity). Interacts with CLEC12B (via ITIM motif); this interaction triggers dephosphorylation and activation of PTPN11. Highly expressed in brain, heart and kidney. The SH2 domains repress phosphatase activity. Binding of these domains to phosphotyrosine-containing proteins relieves this auto-inhibition, possibly by inducing a conformational change in the enzyme. Phosphorylated on Tyr-542 and Tyr-580 upon receptor protein tyrosine kinase activation; which creates a binding site for GRB2 and other SH2-containing proteins. Phosphorylated upon activation of the receptor-type kinase FLT3. Phosphorylated by activated PDGFRB (By similarity). Phosphorylated upon activation of the receptor-type kinase PDGFRA. Conditional deletion in limb and head mesenchyme leads to increased cartilage mass and deficient ossification: osteochondroprogenitors become chondrocytes and not osteoblasts caused by inability of PTPN11/SHP2 to mediate tyrosine dephosphorylation of SOX9. Belongs to the protein-tyrosine phosphatase family. Non-receptor class 2 subfamily.