Reactome: A Curated Pathway Database
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Lectin pathway of complement activation

Stable Identifier
R-HSA-166662
Type
Pathway
Species
Homo sapiens
Locations in the PathwayBrowser
Summation

Activation of the lectin pathway (LP) is initiated by Mannose-binding lectin (MBL), the hetero-complex CL-LK formed from COLEC11 (Collectin liver 1, CL-L1) and COLEC10 (Collectin kidney 1, CL-K1), and the ficolins (FCN1, FCN2, FCN3). All are Ca-dependent (C-type) lectins that initiate the complement cascade after binding to specific carbohydrate patterns on the target cell surface. All form trimers and larger oligomers (Jensen et al. 2005, Dommett et al. 2006, Garlatti et al. 2010). MBL and ficolins circulate in plasma as complexes with homodimers of MBL-associated serine proteases (MASP) (Fujita et al. 2004, Hajela et al. 2002). MASP1, MASP2 and MASP3 have all been reported to mediate complement activation. Upon binding of human lectin to the target surface, the complex of lectin:MASP undergoes conformational changes that result in MASP cleavage and activation (Matsushita M et al. 2000, Fujita et al. 2004). Active MASP2 cleaves C4 to generate C4a and C4b. C4b binds to the target cell surface via its thioester bond, then binds circulating C2 (Law and Dodds 1997). Bound C2 is cleaved by MASP2 to yield the C3 convertase C4b:C2a. The active form of MASP1 was reported to cleave C2 in a manner similar to MASP2 (Matsushita et al. 2000, Chen & Wallis 2004). MASP1 can cleave proenzyme MASP2, leading to complement activation (Heja et al. 2012). MASP1 can also cleave fibrinogen to yield fibrinopeptide B, and activates factor XIII. MASP1 may have a role in removal of 'dead C3', i.e. C3(H2O) (Hajela et al. 2002). In addition to MASP1 to 3, two alternatively-slpiced forms of MASP1 (MAp44) and MASP2 (sMAP) have been implicated in complement cascade signaling (Takahashi et al. 1999, Degn et al. 2010). The functions of MASP3, sMAP and MAp44 in the lectin pathway remain to be clarified.

Literature References
Participants
Participant Of
Orthologous Events
Cross References
BioModels Database