Abl and Src-family kinases also have opposing effects on the actin cytoskeleton (Abl stabilizes/Src destabilizes) and cell migration (Abl inhibits/ Src promotes). Signaling complexes that regulate focal adhesions are known to contain Abl and Src-family kinases, as well as substrates for both kinases [85-87]. Abl, Fyn and their substrates are associated with signaling complexes that organize N-WASP and Arp2/3 at the cell membrane. As members of this complex, Abl and Fyn play opposing roles in regulating actin assembly and remodeling. Fyn recruits and activates N-WASP and ARP2/3 which initiates actin polymerization. Abl inhibits actin polymerization by phosphorylating and inhibiting enabled (Ena) and activating profillin. Abl also strengthens focal contacts by inhibiting their breakdown through an unidentified mechanism. This is may be due to inhibition of Fyn through recruitment of Csk. Transient Src-family kinase activity is required for focal adhesion turnover and membrane extension during actin remodeling. Caveolin phosphorylation and recruitment of Csk represent a mechanism through which temporal and spatial regulation of Src-family kinase activity could be achieved during cell migration to allow transient activation then rapid Csk-induced inactivation of Src-family kinases. Stimulation of caveolin phosphorylation through recruitment/activation of Abl would inhibit Src-family kinase activity at focal contacts, stabilizing these structures.
Was this article helpful?
This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.