Pytowski B, Hicklin D J, Kornhaber G, Dellaratta D V, Witte L
ImClone Systems Incorporated, New York, New York, 10014, USA.
Arch Biochem Biophys. 1998 Nov 15;359(2):310-9. doi: 10.1006/abbi.1998.0907.
Protein kinases play a major role in the regulation of cellular growth. We isolated a murine cDNA encoding a novel serine/threonine kinase (referred to as mSLK) ubiquituously expressed during all stages of murine development and in all adult tissues examined. The cDNA codes for a 1233-amino-acid polypeptide characterized by an N-terminal catalytic domain and a large C-terminal region of unknown function. The sequence of the catalytic domain places mSLK in the STE20 family of cytoplasmic kinases. The noncatalytic domain does not show significant homology to any known protein. mSLK expressed in either COS7 cells or in bacteria was shown to contain kinase activity. The N-terminal fragment of mSLK was able to autophosphorylate on serine and threonine residues, phosphorylate threonine residues on a C-terminal fragment of the molecule, and phosphorylate exogenous substrates myelin basic protein and histone III in vitro. Furthermore, autophosphorylation of the catalytic domain was enhanced in the presence of the C-terminal fragment, which suggests a possible regulatory role for the C-terminal region of mSLK. A genomic clone of mSLK was isolated and used for fluorescence in situ hybridization locating the mSLK gene on band D2 of mouse chromosome 19.
蛋白激酶在细胞生长调节中起主要作用。我们分离出一个小鼠cDNA，它编码一种新型丝氨酸/苏氨酸激酶（称为mSLK），在小鼠发育的所有阶段以及所检测的所有成年组织中均普遍表达。该cDNA编码一个1233个氨基酸的多肽，其特征是具有一个N端催化结构域和一个功能未知的大的C端区域。催化结构域的序列将mSLK置于细胞质激酶的STE20家族中。非催化结构域与任何已知蛋白质均无明显同源性。在COS7细胞或细菌中表达的mSLK显示具有激酶活性。mSLK的N端片段能够在丝氨酸和苏氨酸残基上进行自磷酸化，使分子C端片段上的苏氨酸残基磷酸化，并在体外使外源性底物髓鞘碱性蛋白和组蛋白III磷酸化。此外，在C端片段存在的情况下，催化结构域的自磷酸化增强，这表明mSLK的C端区域可能具有调节作用。分离出mSLK的基因组克隆，并将其用于荧光原位杂交，将mSLK基因定位在小鼠19号染色体的D2带上。
