Oh E S, Woods A, Couchman J R
Department of Cell Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
J Biol Chem. 1997 Mar 28;272(13):8133-6. doi: 10.1074/jbc.272.13.8133.
During cell-matrix adhesion, both tyrosine and serine/threonine kinases are activated. Integrin ligation correlates with tyrosine phosphorylation, whereas the later stages of spreading and focal adhesion and stress fiber formation in primary fibroblasts requires interactions of cell surface proteoglycan with heparin-binding moieties. This correlates with protein kinase C (PKC) activation, and PKCalpha can become localized to focal adhesions in normal, but not transformed, cells. PKC activation has been thought to be downstream of initial receptor-ligand interactions. We now show, however, that syndecan-4 transmembrane heparan sulfate proteoglycan and PKC co-immunoprecipitate and co-patch in vivo. The core protein of syndecan-4 can directly bind the catalytic domain of PKCalpha and potentiate its activation by phospholipid mediators. It can also directly activate PKCalpha in the absence of other mediators. This activity resides in the sequence LGKKPIYKK in the center of the short cytoplasmic domain, and other syndecans lack this sequence and PKC regulatory properties. Syndecan-4 is a focal adhesion component, and this interaction may both localize PKC and amplify its activity at sites of forming adhesions. This represents the first report of direct transmembrane signaling through cell surface proteoglycans.
在细胞与基质黏附过程中，酪氨酸激酶和丝氨酸/苏氨酸激酶均被激活。整合素连接与酪氨酸磷酸化相关，而原代成纤维细胞铺展、黏着斑形成及应力纤维形成的后期阶段需要细胞表面蛋白聚糖与肝素结合部分之间的相互作用。这与蛋白激酶C（PKC）的激活相关，并且PKCα在正常而非转化细胞中可定位于黏着斑。PKC的激活一直被认为是初始受体 - 配体相互作用的下游事件。然而，我们现在发现，Syndecan - 4跨膜硫酸乙酰肝素蛋白聚糖和PKC在体内可共同免疫沉淀并共同形成斑块。Syndecan - 4的核心蛋白可直接结合PKCα的催化结构域，并增强其被磷脂介质激活的能力。在没有其他介质的情况下，它也能直接激活PKCα。这种活性存在于短细胞质结构域中心的LGKKPIYKK序列中，而其他Syndecan蛋白缺乏该序列及PKC调节特性。Syndecan - 4是黏着斑的一个组成部分, 这种相互作用可能既使PKC定位，又在黏附形成部位放大其活性。这是通过细胞表面蛋白聚糖进行直接跨膜信号传导的首次报道。
