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Rho GTPases, which are activated by specific guanine-nucleotide exchange factors (GEFs), play pivotal roles in several cellular functions. TEM4, encoding a protein containing 1510 amino acids, contains a RhoGEF-specific Dbl homology (DH) domain but lacks their typical pleckstrin homology domain. TEM4 is a Rho-specific GEF with novel structural and regulatory properties and predominant expression in the heart. It couples tyrosine kinase signals with the activation of the rho/rac GTPases, thus leading to cell differentiation and/or proliferation. Elevated levels of TEM4, TEM5, TEM6, TEM7 and TEM7R were also raised in breast cancer tissues. TEM4 could also prove to be useful targets therapeutically.
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