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Lad & Lime: Novel Adaptor Proteins involved in T cell Activation

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  • 2014-01-15

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Lad & Lime: Novel Adaptor Proteins involved in T cell Activation and Migration


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- 일시 : 2001년 5월 4일(금) 오후 1시 15분



- 연사 : 윤영대 교수 (이화여대)



- 장소 : 화학관 408호 멀티미디어실



- 문의처 : 류성호 교수 (279-2292)


 


- Abstract



T cell specific src-type tyrosine kinase Lck, plays crucial roles in


T cell activation, development, migration and proliferation. The


functions of Lck requires both the kinase and the regulatory domain,


namely the SH2 domain. To clarify the action mechanism of the Lck SH2


domain in T cell signaling, we screened the binding partners of the Lck


SH2 domain and identified two novel adaptor proteins the functions of which are described below.


A. LAD (Lck Adaptor): Lad was identified as a T cell specific protein containing several protein to protein interaction motifs such as an SH2 domain, an SH3 binding proline-rich motif as well as several phosphotyrosine sites. Furthermore, Lad was tyrosine phosphorylated by and associated with Lck in vivo and redistributed from the cytoplasm to the plasma membrane upon CD3-crosslinking of T cells. More importantly, interlekin-2 (IL-2) promoter activity was enhanced upon overexpression of wild type Lad, but was inhibited by the overexpression of Lad antisense RNA or the dominant negative form of Lad. These characteristics of Lad indicate that Lad plays an essential role as an adaptor protein in Lck-mediated T cell signaling.


 In addition, we have recently found that Lad interacts with G protin beta subunit upon treatment with chemokines, such as Rantes and SDF-1. Moreover, in response to chemokines, Lad recruits FAK and Lck and regulates migation of T cells toward chemokine gradient



B. LIME (Lck Interacting Membrane protein): LIME was identified as a T cell-specific protein of 32Kd. LIME contains a transmembrane domain at the N-terminus and a proline-rich SH3 binding motif as well as multiple phosphotyrosine sites in the cytoplasmic domain. As expected from the sequence, LIME is localized in the plasma membrane and is associated with and phosphorylated by Lck in vivo. Overexpression of LIME led to the enhanced IL-2 promoter activity and the CD3 crosslinking-induced IL2 promoter activity was inhibited by the overexpression of the dominant negative form of LIME. These results indicate that LIME is an essential transmembrane adaptor protein involved in membrane-proximal T cell signaling. Of note is that the structural characteristics of LIME is reminescent of recently cloned T cell-specific adaptor protein, LAT(pp36/38) and TRIM.


In addition, we have recently found that LIME interacts with various SH2 domain-containing proteins, such as Vav, Nck, Grb2, GRID, SAP and SHP-1.



 



 




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