Tyrosine-protein phosphatase non-receptor type 6 (SHP-1) (SHP-1)

Tyrosine-protein phosphatase non-receptor type 6 (SHP-1) is a member of the protein tyrosine phosphatase (PTP) family, primarily expressed in hematopoietic cells [4, 13]. It contains two Src homology 2 (SH2) domains that allow it to interact with tyrosine-phosphorylated receptors and signaling proteins, such as the T-cell receptor (TCR) and B-cell receptor (BCR) [11, 12]. SHP-1 generally functions as a negative regulator of signal transduction by dephosphorylating key signaling molecules like Lck, Zap70, and JAK kinases, thereby modulating immune cell activation, proliferation, and survival [1, 15, 16]. In many hematological malignancies, SHP-1 acts as a tumor suppressor, and its expression is often silenced through promoter hypermethylation [11, 13]. Conversely, in some solid tumors, it may exhibit oncogenic properties or be overexpressed [9, 13]. Therapeutic approaches targeting SHP-1 include the development of small-molecule inhibitors to boost anti-tumor immunity and activators to suppress oncogenic signaling in specific cancers [3, 5, 7]. However, pharmacological modulation of SHP-1 faces challenges, including the risk of inducing systemic inflammation or autoimmunity, as evidenced by the severe phenotypes of SHP-1-deficient mice [1, 11, 14].

Other names

SHP1PTPN6HCPPTP-1CSH-PTP1SHPTP1Hematopoietic cell protein-tyrosine phosphatase

Phosphatase inhibition to enhance immune cell activation; phosphatase activation to suppress oncogenic signaling; dephosphorylation of signaling proteins such as JAK, STAT, and Lck [3, 5, 7, 15].