Human CASK/LIN-2 binds syndecan-2 and protein 4.1 and localizes to the basolateral membrane of epithelial cells.
Human CASK/LIN-2 binds syndecan-2 and protein 4.1 and localizes to the basolateral membrane of epithelial cells.
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人桶/lin-2结合Syndecan-2和蛋白4.1，并定位在上皮细胞的基底外侧膜上。
DOI：
10.1083/jcb.142.1.129
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发表时间：
1998-07-13
影响因子：
7.8
通讯作者：
Anderson, JM
中科院分区：
文献类型：
--
作者：
Cohen, AR;Wood, DF;Marfatia, SM;Walther, Z;Chishti, AH;Anderson, JM
在秀丽隐杆线虫中，lin-2基因突变使外阴细胞分化所需的LET-23受体酪氨酸激酶/Ras/MAP激酶通路失活。LIN-2的一个功能是将LET-23定位到外阴前体细胞的基膜结构域。LIN-2属于膜相关鸟苷酸激酶蛋白家族。我们已经克隆并鉴定了LIN-2的人类同源物，称为hCASK， Northern和Western blot分析显示它是普遍表达的。间接免疫荧光将CASK定位于不同上皮细胞类型的不同侧边和/或基底质膜结构域。我们在酵母双杂交筛选中检测到hCASK的PDZ结构域与硫酸肝素蛋白聚糖syndecan-2结合。这种相互作用通过体外结合试验和免疫荧光共定位得到证实。此外，我们证明hCASK与肌动蛋白结合蛋白4.1结合。Syndecans已知结合细胞外基质，并与受体酪氨酸激酶形成辅受体复合物。我们推测CASK通过与syndecan和protein 4.1的相互作用介导了细胞外基质和肌动蛋白骨架之间的联系。与其他膜相关鸟苷酸激酶一样，其多结构域结构使其能够在膜上充当支架，潜在地招募多种蛋白质并协调信号转导。
In Caenorhabditis elegans, mutations in the lin-2 gene inactivate the LET-23 receptor tyrosine kinase/Ras/MAP kinase pathway required for vulval cell differentiation. One function of LIN-2 is to localize LET-23 to the basal membrane domain of vulval precursor cells. LIN-2 belongs to the membrane-associated guanylate kinase family of proteins. We have cloned and characterized the human homolog of LIN-2, termed hCASK, and Northern and Western blot analyses reveal that it is ubiquitously expressed. Indirect immunofluorescence localizes CASK to distinct lateral and/or basal plasma membrane domains in different epithelial cell types. We detect in a yeast two-hybrid screen that the PDZ domain of hCASK binds to the heparan sulfate proteoglycan syndecan-2. This interaction is confirmed using in vitro binding assays and immunofluorescent colocalization. Furthermore, we demonstrate that hCASK binds the actin-binding protein 4.1. Syndecans are known to bind extracellular matrix, and to form coreceptor complexes with receptor tyrosine kinases. We speculate that CASK mediates a link between the extracellular matrix and the actin cytoskeleton via its interaction with syndecan and with protein 4.1. Like other membrane-associated guanylate kinases, its multidomain structure enables it to act as a scaffold at the membrane, potentially recruiting multiple proteins and coordinating signal transduction.
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DOI：
10.1083/jcb.136.3.669
发表时间：
1997-02-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kim E;Naisbitt S;Hsueh YP;Rao A;Rothschild A;Craig AM;Sheng M
通讯作者：
Sheng M
DOI：
10.1073/pnas.84.16.5962
发表时间：
1987-08-01
影响因子：
11.1
作者：
LIN, CR;KAPILOFF, MS;ROSENFELD, MG
通讯作者：
ROSENFELD, MG
影响因子：
64.8
作者：
KIM, E;NIETHAMMER, M;SHENG, M
通讯作者：
SHENG, M
影响因子：
7.8
作者：
CAREY, DJ;EVANS, DM;CIZMECISMITH, G
通讯作者：
CIZMECISMITH, G
影响因子：
9.2
作者：
Fanning, AS;Anderson, JM
通讯作者：
Anderson, JM