Rap1, referred to as Ras-associated protein 1, is a small G protein that belongs to the Ras superfamily. Rap1 has two isoforms: Rap1A and Rap1B. Like other G proteins, Rap1 is active when bound to GTP but inactive when bound to GDP.
In the Rap1 signaling pathway, the activation of Rap1 by some stimuli recruits many effectors, leading to its involvement in integrin signaling, ERK activation, and other important cellular processes.
The Rap1 signaling pathway exists in many important cellular processes such as the information and control of cell adhesion and cell junction, cell migration, polarization, and cell proliferation ＆ survival.
Rap1 usually binds to GDP and is under an inactive form of Rap1-GDP. Rap1 is activated when GTP replaces GDP in the complex Rap1-GDP through guanylate exchange factors (GEFs). While GAP (GTPase activating protein) deactivates active Rap1-GTP. By switching between the two conformations, Rap1 acts as a molecular switch that regulates the cell's response to external stimuli.
The second messenger cAMP stimulates Epac1, one of RapGEFs, which activates Epac1 to relocate to the plasma membrane, activating Epac-Rap1 signal and enhancing integrin-mediated cell adhesion. And Rap1 interacts with Tiam1 and Vav2 to activate Rac and CDC42, modulating cell polarization and movement. Furthermore, B-Raf, the Rap1 effector, can mediate ERK activation, which triggers the Rap1-MAPK signaling pathway, regulating cell proliferation and survival. In addition, the regulation of PI3K/Akt by Rap1 is also an important mechanism in the control of cell survival and proliferation.
When Rap1GAP and SIPA1, the inhibitors of Rap1, bind to Rap1, Rap1-GTP recovers to inactive Rap1-GDP, ending cellular responses to various stimuli.
As everyone knows, metastasis and invasion of tumor cells are the main causes of death of most cancers. Rap1 is a crucial player in the process of tumor cell migration, invasion, and metastasis. Rap1 plays an important role in tumor progression. And Rap1 is found to be over-activated in many kinds of tumors and is involved in the initiation, development, and metastasis of certain tumors such as breast cancer, prostate cancer, pancreatic cancer, and melanoma. But Rap1 has the opposite effect in the cancers of bladder, lung, and brain.
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