Anti-ACK1/TNK2 Antibody Picoband® Fluoro488 Conjugated

Activated CDC42 kinase 1, also known as ACK1, is an enzyme that in humans is encoded by the TNK2 gene. This gene encodes a tyrosine kinase that binds Cdc42Hs in its GTP-bound form and inhibits both the intrinsic and GTPase-activating protein (GAP) -stimulated GTPase activity of Cdc42Hs. This binding is mediated by a unique sequence of 47 amino acids C-terminal to an SH3 domain. The protein may be involved in a regulatory mechanism that sustains the GTP-bound active form of Cdc42Hs and which is ly linked to a tyrosine phosphorylation signal transduction pathway. Several alternatively spliced transcript variants have been identified from this gene, but the full-length nature of only two transcript variants has been determined.

Isoform 2 and isoform 3 function as proton-gated sodium channels; they are activated by a drop of the extracellular pH and then become rapidly desensitized. The channel generates a biphasic current with a fast inactivating and a slow sustained phase. Has high selectivity for sodium ions and can also transport lithium ions with high efficiency. Isoform 2 can also transport potassium, but with lower efficiency. It is nearly impermeable to the larger rubidium and cesium ions. Isoform 3 can also transport calcium ions. Mediates glutamate-independent Ca2+entry into neurons upon acidosis. This Ca2+overloading is toxic for cortical neurons and may be in part responsible for ischemic brain injury. Heteromeric channel assembly seems to modulate channel properties. Functions as a postsynaptic proton receptor that influences intracellular Ca2+concentration and calmodulin-dependent protein kinase II phosphorylation and thereby the density of dendritic spines. Modulates activity in the circuits underlying innate fear.

1. Hitomi, Y., Heinzen, E. L., Donatello, S., Dahl, H.-H., Damiano, J. A., McMahon, J. M., Berkovic, S. F., Scheffer, I. E., Legros, B., Rai, M., Weckhuysen, S., Suls, A., De Jonghe, P., Pandolfo, M., Goldstein, D. B., Van Bogaert, P., Depondt, C. Mutations in TNK2 in severe autosomal recessive infantile onset epilepsy. Ann. Neurol. 74: 496-501, 2013. 2. La Torre, A., del Rio, J. A., Soriano, E., Urena, J. M. Expression pattern of ACK1 tyrosine kinase during brain development in the mouse. Gene Expr. Patterns 6: 886-892, 2006. 3. Manser, E., Leung, T., Salihuddin, H., Tan, L., Lim, L. A non-receptor tyrosine kinase that inhibits the GTPase activity of p21cdc42. Nature 363: 364-367, 1993.