WNT 介导的 DVL 激活
中文名称
通路描述
三个人类 Dishevelled (DVL) 蛋白在 WNT 信号通路的转导中发挥核心和重叠作用 (Lee et al, 2008; 综述于 Gao and Chen 2010)。DVL 活性受磷酸化调节，尽管细节尚未完全阐明。DVL 即使在无 WNT 刺激的情况下也可能以磷酸化蛋白形式存在，并在配体结合时进一步磷酸化。已报道 CSNK1E、CSNK2 和 PAR1 可磷酸化 DVL (Willert et al, 1997; Sun et al, 2001; Cong et al, 2004; Ossipova et al, 2005)。在通路激活后，磷酸化的 DVL 通过 DVL PDZ 域与 FZD KTxxxW 基序之间的相互作用转运至细胞膜 (Wong et al, 2003; Umbhauer et al, 2000; Kikuchi et al, 2011)。在细胞膜上，DVL 被认为通过其 DIX 域寡聚化，为 AXIN 招募提供平台；AXIN 的招募也通过与 LRP 相互作用而促进 (Schwarz-Romond et al, 2007; Mao et al, 2001)。DVL 与磷脂酰肌醇 -4-激酶 II (PI4KII) 和磷脂酰肌醇 -4-磷酸 5-激酶 I (PIP5KI) 相互作用，促进膜上磷脂酰肌醇 4,5-双磷酸 (PI(4,5)P2) 的形成，这是 LRP6 聚类和磷酸化以及 AXIN 招募所必需的 (Pan et al, 2008; Qin et al, 2009)。
英文描述
Regulation of Complement cascade Two inherent features of complement activation make its regulation very important:
1. There is an inherent positive feedback loop because the product of C3 activation forms part of an enzyme that causes more C3 activation.
2. There is continuous low-level activation of the alternative pathway (see Spontaneous hydrolysis of C3 thioester).
Complement cascade activation is regulated by a family of related proteins termed the regulators of complement activation (RCA). These are expressed on healthy host cells. Most pathogens do not express RCA proteins on their surface, but many have found ways to evade the complement system by stably binding the RCA that circulates in human plasma (Lambris et al. 2008); trapping RCA is by far the most widely employed strategy for avoiding the complement response. RCA recruitment is common in bacteria such as E. coli and streptococci (Kraiczy & Wurzner 2006) and has also been described for viruses, fungi and parasites. RCA deposition and the complement system also have an important role in tissue homeostasis, clearing dead cells and debris, and preventing damage from oxidative stress (Weismann et al. 2011).
RCA proteins control complement activation in two different ways; by promoting the irreversible dissociation (decay acceleration) of complement convertases and by acting as cofactors for Complement factor I (CFI)-mediated cleavage of C3b and C4b.
Decay accelerating factor (DAF, CD55), Complement factor H (FH), Membrane Cofactor Protein (MCP) and Complement receptor 1 (CR1) are composed of arrays of tandem globular domains termed CCPs (complement control protein repeats) or SCRs (short consensus repeats). CR1, MCP and FH are cofactors for the CFI-mediated cleavage of C3b, generating iC3b. CR1 and MCP are also cofactors for C4b cleavage.
C4BP is an additional cofactor for the CFI-mediated cleavage of C4b.
1. There is an inherent positive feedback loop because the product of C3 activation forms part of an enzyme that causes more C3 activation.
2. There is continuous low-level activation of the alternative pathway (see Spontaneous hydrolysis of C3 thioester).
Complement cascade activation is regulated by a family of related proteins termed the regulators of complement activation (RCA). These are expressed on healthy host cells. Most pathogens do not express RCA proteins on their surface, but many have found ways to evade the complement system by stably binding the RCA that circulates in human plasma (Lambris et al. 2008); trapping RCA is by far the most widely employed strategy for avoiding the complement response. RCA recruitment is common in bacteria such as E. coli and streptococci (Kraiczy & Wurzner 2006) and has also been described for viruses, fungi and parasites. RCA deposition and the complement system also have an important role in tissue homeostasis, clearing dead cells and debris, and preventing damage from oxidative stress (Weismann et al. 2011).
RCA proteins control complement activation in two different ways; by promoting the irreversible dissociation (decay acceleration) of complement convertases and by acting as cofactors for Complement factor I (CFI)-mediated cleavage of C3b and C4b.
Decay accelerating factor (DAF, CD55), Complement factor H (FH), Membrane Cofactor Protein (MCP) and Complement receptor 1 (CR1) are composed of arrays of tandem globular domains termed CCPs (complement control protein repeats) or SCRs (short consensus repeats). CR1, MCP and FH are cofactors for the CFI-mediated cleavage of C3b, generating iC3b. CR1 and MCP are also cofactors for C4b cleavage.
C4BP is an additional cofactor for the CFI-mediated cleavage of C4b.
所含基因
55 个基因