Reversible tyrosine phosphorylation/dephosphorylation of proline-directed protein kinase FA/glycogen synthase kinase-3α in A431 cells

✍ Scribed by Jau-Song Yu; Hsiang-Ching Chen; Shiaw-Der Yang

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 287 KB
• Volume: 171
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/(sici)1097-4652(199704)171:1<95::aid-jcp11>3.0.co;2-n

✦ Synopsis

Modulation of protein kinase FA/glycogen synthase kinase-3a (kinase FA/GSK-3a) by reversible tyrosine phosphorylation/dephosphorylation was investigated. In addition to genistein, other protein tyrosine kinase (PTK) inhibitors, such as tyrphostin A47 and B42, also could induce tyrosine dephosphorylation and inactivation of kinase FA/GSK-3a in A431 cells, and this process was found to be reversible. Pretreatment of the cells with 100 mM orthovanadate, a protein tyrosine phosphatase (PTP) inhibitor, could diminish significantly the effects of PTK inhibitors on both enzyme activity and phosphotyrosine content of the kinase, suggesting that the PTK inhibitors induced tyrosine dephosphorylation/inactivation of this kinase is mediated by orthovanadate-sensitive PTP(s) in A431 cells. Moreover, the phosphotyrosine moiety of kinase FA/GSK-3a was found to be highly turned over in resting cells. Interestingly, we found that the less active, tyrosinedephosphorylated form of kinase FA/GSK-3a immunoprecipitated from genisteintreated cells was able to reactivate partially with concomitant rephosphorylation of tyrosine residue in vitro. Taken together, these findings demonstrate that tyrosine phosphorylation and concomitant activation of kinase FA/GSK-3a can be carried out both in vitro and in vivo and an in vivo phosphatase activity may function in antagonism to PTK activation of kinase FA/GSK-3a.