Csk是Y505的磷酸化激酶（负调控Lck活性），CD45则负责去磷酸化激活Lck。CD45是几乎所有白细胞都表达的一类跨膜蛋白，其胞内部分具有磷酸水解酶活性。去磷酸化后的Lck处于半开放状态，需要其他磷酸激酶或者自己磷酸化Y394而进入激活状态。 Lck的结构与激活方式。

2020年6月21日 · 蛋白酪氨酸磷酸酶CD45可以使Lck的C端Y505去磷酸化，从而使Lck可以通过反式自磷酸化激活。 当CD45缺陷时，Lck处于自抑制失活构象，TCR信号减弱，胸腺发育受阻。

When cells are CD45 deficient, low basally active Lck amounts propagate through the system. These findings highlight the importance of the positive regulatory role of CD45 upon Lck activation at high levels of Csk activity and of its negative regulatory roles, such as ζ-chain dephosphorylation, at low levels Csk activity.

2002年12月23日 · We propose that truncation of the CD45 ectodomain reduced the access of CD45 to Lck in GEMs, which increased the closed pTyr 505 form of Lck, thereby resulting in decreased amounts of ...

2017年8月3日 · Our findings reveal that modification of Y192 inhibits the ability of CD45 to associate with Lck in cells and dephosphorylate the C-terminal tail of Lck, which prevents its adoption of an active open conformation. These results suggest a negative feedback loop that responds to signaling events that tune active Lck amounts and TCR sensitivity.

To investigate this question, we have reconstituted CD45 (encoded by Ptprc)-deficient mice, which display severe defects in thymic development, with five different expression levels of transgenic CD45RO, or with mutant PTPase null or PTPase-low CD45R0.

We propose that high wild-type CD45 expression is necessary to dephosphorylate p56 (lck) pTyr-394, suppressing CD4 T+ cell lineage commitment and hyperactivity. The molecular mechanisms whereby the CD45 tyrosine phosphatase (PTPase) regulates T cell receptor (TCR) signaling responses remain to be elucidated.

2019年10月22日 · T cells require the protein tyrosine phosphatase CD45 to detect and respond to antigen because it activates the Src family kinase Lck, which phosphorylates the T cell antigen receptor (TCR) complex. CD45 activates Lck by opposing the negative regulatory kinase Csk. Paradoxically, CD45 has also been …

2014年10月10日 · T cell receptor (TCR) phosphorylation requires the kinase Lck and phosphatase CD45. CD45 activates Lck by dephosphorylating an inhibitory tyrosine of Lck to relieve autoinhibition. However, CD45 also dephosphorylates the TCR, and the spatial exclusion of CD45 from TCR clustering in the plasma membra …

2004年1月30日 · CD45 is a transmembrane, two-domain protein-tyrosine phosphatase expressed exclusively in nucleated hematopoietic cells. The Src family kinase, Lck, is a major CD45 substrate in T cells and CD45 dephosphorylation of Lck is …