HSPB6-induced smooth muscle relaxation

Proposed mechanism of HSPB6-induced smooth muscle relaxation. Activation of adenylate cyclase (AC) by prostaglandin (PG), forskolin (FSK), or isoproterenol (ISO) increases the levels of cyclic adenosine monophosphate (cAMP). Activation of guanylate cyclase (GC) by nitric oxide (NO), sodium nitroprusside (SNP), or natriuretic peptides leads to increased levels of cyclic guanosine monophosphate (cGMP). Cyclic AMP and GMP can be degraded by phosphodiesterases (PDEs). Increased cAMP and cGMP levels activate cAMP-dependent protein kinase and cGMP-dependent protein kinase (PK), respectively. HSPB6 is phosphorylated by cGMP-dependent or cAMP-dependent protein kinase on serine 16 (pHSPB6). Phosphorylation of HSPB6 on serine 16 is associated with vasorelaxation. The HSPB6 phosphopeptide (YARAAARQARAWLRRApSAPLPGLK) treatment of precontracted isolated smooth muscle tissue circumvents the cyclic nucleotide signaling pathway by first directly crossing the cell membrane (1). Endogenous phosphorylated HSPB6 or the HSPB6 phosphopeptide displaces phosphocofilin from a complex with 14-3-3 forming phospho-HSPB6-14-3-3 complex (2). The displaced phosphocofilin is dephosphorylated by phosphatases such as slingshot or chronophin (3). Dephosphorylated cofilin induces actin depolymerization resulting in stress fiber disruption in smooth muscle cells and induces relaxation in smooth muscle (4)

Publication

The small heat shock protein, HSPB6, in muscle function and disease. (2010) Catherine M. Dreiza, et al. Cell Stress Chaperones. 2010 Jan;15(1):1-11. Figure: F2. Homo sapiens

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