Pulmonary Arterial Hypertension KnowledgeBase (bioinfom_tsdb)
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Pulmonary Arterial Hypertension KnowledgeBase
General information | Literature | Expression | Regulation | Mutation | Interaction

Basic Information

Gene ID

9901

Name

SRGAP3

Synonymous

ARHGAP14|MEGAP|SRGAP2|WRP;SLIT-ROBO Rho GTPase activating protein 3;SRGAP3;SLIT-ROBO Rho GTPase activating protein 3

Definition

SLIT-ROBO Rho GTPase activating protein 2|SLIT-ROBO Rho GTPase-activating protein 3|WAVE-associated Rac GTPase activating protein|mental disorder-associated GAP|rho GTPase-activating protein 14

Position

3p25.3

Gene type

protein-coding

Title

Abstract

A tumor suppressor role for srGAP3 in mammary epithelial cells.

srGAP3, a member of the Slit-Robo sub-family of Rho GTPase-activating proteins (Rho GAPs), controls actin and microtubule dynamics through negative regulation of Rac. Here, we describe a potential role for srGAP3 as a tumor suppressor in mammary epithelial cells. We show that RNAi-mediated depletion of srGAP3 promotes Rac dependent, anchorage-independent growth of partially transformed human mammary epithelial cells (HMECs). Furthermore, srGAP3 expression is absent, or significantly reduced in 7/10 breast cancer cell lines compared with normal HMECs. Re-expression of srGAP3 in a subset of these cell lines inhibits both anchorage-independent growth and cell invasion in a GAP-dependent manner, and this is accompanied by an increase in phosphorylation of the ezrin/radixin/moesin (ERM) family proteins and myosin light chain 2 (MLC2). Inhibition of the Rho regulated kinase, ROCK, reduces ERM and MLC2 phosphorylation and restores invasion. We conclude that srGAP3 has tumor suppressor-like activity in HMECs, likely through its activity as a negative regulator of Rac1.

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