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8.A.104.  The 5'-AMP-activated protein kinase (AMPK) Family 

This family includes the catalytic subunits of AMP-activated protein kinases (AMPK), energy sensor protein kinases that play key roles in regulating cellular energy metabolism.  Some of these proteins include an N-terminal PKc-like superfamily domain and a C-terminal AMPKA_C-like domain, but other members have only the N-terminal PKc domain.  In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes in mammals (Egan et al. 2011). It acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm (McGee et al. 2008). It also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1 (Hallows et al. 2003).  It plays a role in the differential regulation of pro-autophagy (composed of PIK3C3, BECN1, PIK3R4 and UVRAG or ATG14) and non-autophagy (composed of PIK3C3, BECN1 and PIK3R4) complexes in response to glucose starvation, and can inhibit the non-autophagy complex by phosphorylating PIK3C3 while activating the pro-autophagy complex by phosphorylating BECN1.

A review summarizes the role of AMPK in the regulation of renal epithelial transport, updates the growing list of AMPK transport protein targets and discusses the regulatory mechanisms involved (Pastor-Soler and Hallows 2012). It couples membrane transport to the metabolic status of epithelial tissues like the kidney. AMPK is also involved in the coordination of hormonal, inflammatory, and other cellular stress pathway signals to produce an integrated effect on tubular transport (Pastor-Soler and Hallows 2012).  Mackenzie and Elliott 2014 review the roll of AMPK in glucose uptake and focus on a mechanism that operates via an insulin-dependent pathway.

This family belongs to the: Protein Kinase (PK) Superfamily.

References associated with 8.A.104 family:

Egan, D.F., D.B. Shackelford, M.M. Mihaylova, S. Gelino, R.A. Kohnz, W. Mair, D.S. Vasquez, A. Joshi, D.M. Gwinn, R. Taylor, J.M. Asara, J. Fitzpatrick, A. Dillin, B. Viollet, M. Kundu, M. Hansen, and R.J. Shaw. (2011). Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science 331: 456-461. 21205641
Hallows, K.R., G.P. Kobinger, J.M. Wilson, L.A. Witters, and J.K. Foskett. (2003). Physiological modulation of CFTR activity by AMP-activated protein kinase in polarized T84 cells. Am. J. Physiol. Cell Physiol. 284: C1297-1308. 12519745
Mackenzie, R.W. and B.T. Elliott. (2014). Akt/PKB activation and insulin signaling: a novel insulin signaling pathway in the treatment of type 2 diabetes. Diabetes Metab Syndr Obes 7: 55-64. 24611020
McGee, S.L., B.J. van Denderen, K.F. Howlett, J. Mollica, J.D. Schertzer, B.E. Kemp, and M. Hargreaves. (2008). AMP-activated protein kinase regulates GLUT4 transcription by phosphorylating histone deacetylase 5. Diabetes 57: 860-867. 18184930
Pastor-Soler, N.M. and K.R. Hallows. (2012). AMP-activated protein kinase regulation of kidney tubular transport. Curr Opin Nephrol Hypertens 21: 523-533. 22801443