Integrin α9β1 Unique signaling pathways reveal diverse biological roles

Integrins are transmembrane heterodimeric receptors responsible for transducing and modulating signals between the extracellular matrix and cytoskeleton, ultimately influencing cell functions such as adhesion and migration. Integrin alpha 9 beta 1 is classified within a two member sub-family of integrins highlighted in part by its specialized role in cell migration. The importance of this role is demonstrated by its regulation of numerous biological functions including lymphatic valve morphogenesis, lymphangiogenesis, angiogenesis and hematopoietic homeostasis. Compared to other integrins the signaling mechanisms that transduce alpha 9 beta 1-induced cell migration are not well described. We have recently shown that Src tyrosine kinase plays a key proximal role to control alpha 9 beta 1 signaling. Specifically it activates inducible nitric oxide synthase (iNOS) and in turn nitric oxide (NO) production as a means to transduce cell migration. Furthermore, we have also described a role for FAK, Erk and Rac1 in alpha 9 beta 1 signal transduction. Here we provide an over view of known integrin alpha 9 beta 1 signaling pathways and highlight its roles in diverse biological conditions.