The role of small GTPases Rap1 and RhoA in growth hormone signal transduction

Abstract

The small GTPase Ras is one major regulator for GH stimulated p44/42 MAP kinase pathway. The aim of this project was to investigate the role of Ras-related small GTPases Rap1 and RhoA in GH signal transduction. The results showed that GH stimulated CrkII-C3G dependent activation of Rap1 and Rap2. Full activation of CrkII-C3G-Rap1 pathway stimulated by GH required the combined activity of JAK2 and c-Src. This pathway was utilized by GH to switch p44/42 MAP kinase and JNK/SAPK activities and subsequent transactivation. GH also stimulated JAK2 dependent activation of RhoA and its substrate ROCK. RhoA and ROCK activity were required for GH stimulated Stat5 mediated transcription as a consequence of repression of p300 dependent recruitment of HDAC6. Therefore, Rap1 and RhoA are two important signaling molecules in GH stimulated activation of gene transcription.