Endogenous SH2B1 protein localizes to lamellipodia and filopodia: platinum replica electron-microscopy study.

The widely expressed adapter protein SH2B1 was initially identified as a binding partner and substrate of tyrosine kinase JAK2. SH2B1β potentiates JAK2 activation in response to different ligands, including growth hormone, leptin and prolactin. SH2B1β has been implicated in cell motility and regulation of actin rearrangement in response to growth hormone, prolactin and platelet-derived growth factor. Here we use immunofluorescence and platinum replica electron-microscopy (PREM) technique to study localization of endogenous SH2B1. We show that endogenous SH2B localizes to two actin-rich protrusive organelles in cells: lamellipodia and filopodia. Based on this and previously published data, we suggest that at least some SH2B1 isoforms directly bind to actin filaments in both structures. Additionally, SH2B1 isoforms may work as a partner of filamin A in lamellipodia and VASP in filopodia participating in modulation of the actin cytoskeleton in response to extracellular signals.