Plexin-A1, Plexin-A2, and Plexin-B1 (PLXNA1, PLXNA2, PLXNB1)

Plexin-A1, Plexin-A2, and Plexin-B1 are members of the plexin family of large, single-pass transmembrane receptors that serve as the primary signaling components for semaphorin ligands [1, 2, 6]. These receptors are characterized by an extracellular sema domain and an intracellular region containing a split GTPase-activating protein (GAP) domain, which regulates the activity of small GTPases like R-Ras and Rap1 to modulate the cytoskeleton [6, 10, 16]. Plexin-A1 and A2 typically function as co-receptors with neuropilins to transduce signals from secreted class 3 semaphorins, while Plexin-B1 directly binds transmembrane semaphorins such as Sema4D [2, 13, 15]. Biologically, they are critical for axon guidance, vascular development, and immune cell regulation [2, 4, 8]. In disease, dysregulation of these plexins is linked to cancer progression, where they promote tumor cell migration and angiogenesis, as well as neurodegenerative and neurodevelopmental disorders [4, 15, 18, 19]. Therapeutic strategies include monoclonal antibodies and peptides designed to block ligand binding or allosterically modulate receptor activity, with several candidates exploring applications in oncology and inflammatory diseases [1, 3, 9, 17].

Other names

PLXN1NOVPLEXIN-1PLXN2OCTPLXNB1SEPPLXN5

Antagonism of semaphorin-plexin interaction, allosteric inhibition of receptor activity, and agonistic mimicry of semaphorin signaling [1, 3, 9, 17].