Table 1. Phosphatases and their role in B cells, T cells and mast cells.

Phosphatases	B cells	T cells	Mast cells
Tyrosine phosphatases
Receptor protein tyrosine phosphatase
CD45: Receptor-type  tyrosine-protein  phosphatase C	Positively regulates BCR signaling by dephosphorylating the inhibitory tyrosine of Lyn [45•] B cell activation is only partially impaired in CD45−/− B cells due to expression of CD148 [48]	Dual positive and negative regulatory role by being able to dephosphorylate both the inhibitory tyrosine and the activating loop tyrosine of Lck [44,45•] T cell activation is impaired in CD45−/− T cells	Dephosphorylates the inhibitory tyrosine (Y570) of Lyn [49] Degranulation and IL6 secretion are decreased while IL3 and SF dependent-proliferation are enhanced in CD45−/− BMMC [49]
CD148: Receptor-type  tyrosine-protein  phosphatase eta	Positively regulates BCR signaling by dephosphorylating the inhibitory tyrosine of Lyn [48] B cell activation is partially impaired in CD148−/− B cells due to expression of CD45 [48]	Dual positive and negative regulatory role by being able to dephosphorylate both the inhibitory tyrosine and the activating loop tyrosine of Lck [46,47] Not expressed in all T cells [46]	Not reported
PTPα: Receptor-type  tyrosine-protein  phosphatase alpha	Not reported	Lipid raft associated phosphatase that negatively regulates Fyn activity in unstimulated cells by preferentially dephosphorylating the activating loop tyrosine [58]	Lyn, Fyn, Hck, Syk, SHIP, PI3K and MAPK activations are impaired in PTPα−/− BMMC [50•] IgE- induced degranulation, cytokine and cysteinyl leukotriene secretion are enhaced in PTPα−/− [50•] PTPa−/−mice display enhanced IgE-dependent anaphylaxis [50•]
Non-receptor Protein Tyrosine Phosphatase
PTNP22 (PEP/LYP):  Tyrosine-protein  phosphatase non-receptor  type 2	Negatively regulates BCR signaling by directly dephosphorylating Syk. Also reduces PLCγ2, p38 and Akt phosphorylation [54] Autoimmune-associated Lyp620W is a gain of function variant [54] Pep619W knockin mice have hyperresponsive B cells [56••,57•]	LYP (human)/Pep (mouse) dampens TCR signaling by dephosphorylating activating tyrosine of Lck and Fyn and their substrates such as Zap70 [51,52,55] Autoimmune-associated Lyp620W is a gain of function variant [55] Pep619W knockin mice have hyperresponsive T cells [56••,57•]	IgE-dependent degranulation and Ca2+ reponses are reduced in PEP−/− BMMC [53] PLCγ1 Phosphorylation is reduced in PEP−/− BMMC [53] PEP−/− mice display decreased passive anaphylaxis [53]
PTPN2: Tyrosine-protein  phosphatase non-receptor  type 2	Not reported	Negatively regulates TCR signaling by dephosphorylating the activating loop tyrosine of Lck and Fyn [59•]	Not reported
SH2 domain-containing Tyrosine phosphatases
SHP-1: Tyrosine-protein  phosphatase non-receptor  type 6	Negatively regulates BCR signaling by dephosphorylating Igab ITAMs, Lyn, Syk, SLP-65/ BLNK, Vav1 [7,8]	Negatively regulates TCR signaling by dephosphorylating CD3 ITAMs, Lck, Zap70, LAT, SLP-76, Vav1 [61,62•]	Positive and negative regulation of mast cell functions [10,60]
SHP-2: Tyrosine-protein  phosphatase non-receptor  type 11	SHP-2 negatively regulates B cell activation by inhibiting phosphorylation of Igb ITAM, Syk, PLCγ2 and Erk [63]	Indirect evidence suggest that SHP-2 negatively regulates TCR signaling by directly dephosphorylating or indirectly causing reduced phosphorylation of Zap70, Vav, PLCγ1 and Erk [11]	Positively regulates FcεRI-dependent degranulation and TNF-α secretion [13,14] Negatively regulates Kit signaling [15]
Cytosolic Tyrosine Phosphatases lacking SH2 domains
PTP-PEST: Tyrosine-protein  phosphatase non-receptor  type 12	Negatively regulats B cell activation by dephosphorylation of Shc, Pyk2, Fak and Cas, and inactivating the Ras pathway [65]	PTP-PEST can dephosphorylate the activating tyrosine of Lck, reduce Zap70 phosphorylation and inhibit the MAP pathway [66]. It has also been reported to have positive effects by dephosphorylating Pyk2, promoting secondary responses [64•]	Not reported
PTPε Receptor-type  tyrosine-protein  phosphatase epsilon	Not reported	Not reported	IgE-dependent degranulation, cytokine secretion are enhanced in PEPε−/− BMMC [67•] LAT, SLP76 phosphorylation and MAP kinase activation are incresead in PEPε−/− BMMC [67•] PEPε−/− mice undergo increased IgE-induced passive anaphylaxis [67•]
TULA-2: Tyrosine-protein  phosphatase STS1/TULA2	Not reported	Not reported	Negatively regulates FcεRI-dependent degranulation by dephosphorylating Syk and PLCγ2 [68•] Upon FcεRI engagement, TULA-2 forms complex that contains Nck, SHIP1, SLP76 and Grb2 [68•]
Phosphatidate phosphatases
LIPIN-1: Phosphatidate  phosphatase LPIN1	Not reported	Not reported	IgE-dependent degranulation and prostaglandin D2 production are enhanced in Lipin-1 −/− BMMC [69] PKC and SNPA-23 phosphorylation are increased in Lipin-1−/− BMMC [69] Lipin1 deficiency exacerbated passive anaphylaxis reaction in vivo [69]
Lipid Phosphatases
SH2 domain-containing lipid phosphatases
SHIP1: Phosphatidylinositol  3,4,5-trisphosphate  5-phosphatase 1	Negatively regulates BCR signaling by hydrolyzing PI(3,4,5)P3, counteracting the PI3K pathway, resulting in reduced activity of SOS, Vav, PLC-γ, Btk, Akt [16,21,22•]. Inhibits Ras and activation of MAP kinases by recruiting Dok-1 [20]	Negatively regulates TCR signaling by recruiting Dok-1 and Dok-2 to LAT, which in their turn inhibit Akt and Zap70 activity [18]. In vivo T cell specific SHIP-1 mice have relatively normal signaling [19]	Negatively regulates FcεRI-dependent degranulation [17,39,40]
SHIP2: Phosphatidylinositol  3,4,5-trisphosphate  5-phosphatase 2	Negatively regulates BCR signaling by hydrolyzing PI(3,4,5)P3, counteracting the PI3K pathway, resulting in reduced PLCγ, Btk and Akt activity [41]	Not reported	Negatively regulates FcεRI-dependent degranulation and cytokine secretion [42•]
Lipid phosphatase lacking SH2 domains
PTEN: Phosphatase  and tensin homolog	Negatively regulates BCR signaling by hydrolyzing PI(3,4,5)P3, counteracting the PI3K pathway, resulting in reduced Akt activity [72] Suppressor of B cell lymphoma [75•]	Negatively regulates TCR signaling by hydrolyzing PI(3,4,5)P3, counteracting the PI3K pathway, resulting in reduced Akt and Erk activity [73] Suppressor of T lymphoma [74]	Negatively regulates human mast cells activation [70,71] PTEN deficiency causes mast cell hyperplasia and mastocytosis [71]