Table 1.
Protein tyrosine kinases and phosphatases implicated in the regulation of FcγR-mediated phagocytosis and motility of macrophages.
| Kinases | Phagocytosis | Motility | |
|---|---|---|---|
| SFK | Hck | Hck−/−Fgr−/−Lyn−/− BMM show reduced phagocytosis [30, 32]. | Consititutively active form associated with increased motility in vitro [128] and in vivo [129]. Hck−/− macrophages show reduced motility in vitro and in vivo [126]. |
| Fgr | Negatively regulates phagocytosis in associate with SIRPα-SHP-1 complex [97]. | Hck−/−Fgr−/− show reduced migration ability [127]. | |
| Lyn | Hck−/−Fgr−/−Lyn−/− BMM show reduced phagocytosis [30, 32]. | Hck−/−Fgr−/−Lyn−/− BMM show reduced migration ability [194]. | |
| Src | Phosphorylate FcγRIIA in vitro [25]. | Co-immunoprecipitates with WASP, Pyk2, PTP-PEST and PSTPIP in osteoclasts and expression of constitutively active Src increases their phosphorylation [188]. | |
| Fyn | Phosphorylate FcγRIIA in vitro [26]. | Co-immunoprecipitates with Hck, Fgr, Lyn and Fyn in uPA-R complex involved in adhesion and chemotaxis [195]. | |
| Lck | Phosphorylate Vav [44]. | ? | |
| Syk | Syk−/− BMM fail to ingest IgG-coated particles [31, 32]. γ subunit is not phosphorylated in Syk−/− BMM [31]. |
Required for CX3CL1 chemotaxis but not CSF-1 [193]. | |
| Pyk2/FAK | Pyk2 and FAK are activated during phagocytosis [196, 197]. | Pyk2−/− BMM fail to polarize or ruffle [163]. SDF1-α stimulated Pyk2−/− BMM fail to detach from the underlying substrate [163]. FAK−/− BMM show migration defect toward CSF-1, SDF-1α and MCP-1 [171] |
|
| c-Abl | ? | c-Abl and SFK regulate migration and activation of the small GTPases Cdc42 and Rac [198]. | |
| Csk | Csk abolish phagocytosis signaling in a kinase-dependent manner [15] | Overexpression of CSK show enhance effect of MIF-induced MMP-13 expression [199]. | |
| Phosphatases | |||
| SHP-1 | Overexpression of SHP-1 show reduced phagocytic ability [98]. SHP-1 associates with FcγRIIa and this association appears to suppress total cellular tyrosine phosphorylation [2]. Negatively regulates phagocytosis in association with SIRPα [97]. |
SHP-1 deficiency lead to an abundant and exclusive increase in the infiltration of macrophages into the CNS [200]. | |
| PTP-PEST | ? | Reduced expression of PTP-PEST inhibits osteoclast migration towards osteopontin [188]. | |
| PTP-phi | ? | PTP phi induces cell rounding and ruffle formation and dephosphorylates Paxillin in dorsal ruffles [155]. | |
| CD148 | Double deficient BMM of CD148 and CD45 show reduced phagocytosis [17]. | Anti-CD148 antibody inhibits migration of primary macrophages in response to CSF-1 [201] |
FOOTNOTES : ?, Unknown