Studies on a new growth factor under the control of retinoic acid, midkine (MK)

The arrangement of-S-Sbridges in MK was determined as follows：C_&lt；12&gt；-C_&lt；36&gt；，C_&lt；20&gt；-C_&lt；45&gt；，C_&lt；27&gt；-C_&lt；49&gt；，C_&lt；54&gt；-C_&lt；91&gt；，C_&lt；69&gt；-C_&lt；101&gt；，indicating that MK is composed of two domains。The 2kb upstream sequence of mouse MK gene(MK2 Type)was linked to CAT gene and transfected to F9cells。The 2 kd sequence mediated CAT gene activation upon retinoic acid treatment.A retinoic acid responsive enhancer was found in the 2kb fragment。The core element has high dergee of homology to retinoic acid receptor binding sequence，and indeed bound to RXR·RAR heterodimer。MK had neurotrophic activity to various embryonic neurons such as from spinal cord and dorsal root ganglion。MK bound to syndecan and to a putative MK receptor of 85 kDa。MK expression was increased in many human carcinomas including Wilm‘s tumor，hepatocellular carcinoma and pancreatic carcinoma.Senile plaqule in the brain of Arzheimer disease patients invariable expressed MK.As above，MK is an important growth factor under the control of retinoic acid，and is probably involved in ethiology of human diseases。

The arrangement of -S-Sbridges in MK was determined as follows : C_<12>-C_<36>, C_<20>-C_<45>, C_<27>-C_<49>, C_<54>-C_<91>, C_<69>-C_<101>, indicating that MK is composed of two domains. The 2kb upstream sequence of mouse MK gene (MK2 type) was linked to CAT gene and transfected to F9 cells. The 2kd sequence mediated CAT gene activation upon retinoic acid treatment. A retinoic acid responsive enhancer was found in the 2kb fragment. The core element has high dergee of homology to retinoic acid receptor binding sequence, and indeed bound to RXR・RAR heterodimer. MK had neurotrophic activity to various embryonic neurons such as from spinal cord and dorsal root ganglion. MK bound to syndecan and to a putative MK receptor of 85 kDa. MK expression was increased in many human carcinomas including Wilm's tumor, hepatocellular carcinoma and pancreatic carcinoma. Senile plaqule in the brain of Arzheimer disease patients invariable expressed MK.As above, MK is an important growth factor under the control of retinoic acid, and is probably involved in ethiology of human diseases.