Dysfunction of protein kinase FA/GSK-3α in lymphocytes of patients with schizophrenic disorder

✍ Scribed by Dr. Shiaw-Der Yang; Jau-Song Yu; Tsong-Tze Lee; Chuan-Ching Yang; Mei-Hui Ni; Yong-Yi Yang

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 946 KB
• Volume: 59
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.240590112

✦ Synopsis

As compared to normal people, the lymphocytes of patients with schizophrenia were found to have an impairment of ATP.Mg-dependent protein phosphatase activation. More importantly, the impaired protein phosphatase activation in the lymphocytes of schizophrenic patients could be consistently and completely restored to normal by exogenous pure protein kinase FA/glycogen synthase kinase-3a (kinase F A / G S K -~~) (the activating factor of ATP.Mgdependent protein phosphatase), indicating that the molecular mechanism for the impaired protein phosphatase activation in schizophrenic patients may be due to a functional loss of kinase FAIGSK-3a. lmmunoblotting and kinase activity analysis in an anti-kinase FAIGSK-3a immunoprecipitate further demonstrate that both cellular activities and protein levels of kinase F A / G S K -~~ in the lymphocytes of schizophrenic patients were greatly impared as compared to normal controls. Statistical analysis revealed that the lymphocytes isolated from 37 normal people contain kinase F A / G S K -~~ activity in the high levels of 14.8 * 2.4 units/mg of cell protein, whereas the lymphocytes of 48 patients with schizophrenic disorder contain kinase F A / G S K -~~ activity in the low levels of 2.8 ? 1.6 units/mg, indicating that the different levels of kinase F A / G S K -~~ activity between schizophrenic patients and normal people are statistically significant. Taken together, the results provide initial evidence that patients with schizophrenic disorder may have a common impairment in the protein levels and cellular activities of kinase F A I C S K -~~, a multisubstrate protein kinase and a multisubstrate protein phosphatase activator in their lymphocytes.