These data support the hypothesis that HSJ1a can partially rescue the redistribution of a Parkin RING1 domain mutant to impaired mitochondria.
We therefore assessed the ability of the Sse1 mutants to impair [ URE3] propagation using this assay.
Unexpectedly, Kif3a deficiency upregulated Hh signaling and reversed the effect of mutant Pkd1 to impair osteoblastic differentiation and stimulate adipogenesis in vivo and in vitro.
Additionally, IL-10 was ∼2 3 fold upregulated after stimulation with recombinant L. plantarum expressing lipidated (LpA) and the mutant appeared to impair this response (Fig. 7E).
Indeed, it has been shown that the A30P mutant fails to impair the growth of yeast cells [ 35].
Specifically, the T14M/T15K mutant, predicted to impair ATP hydrolysis, as well as the W125D substitution, which deforms and adds charge to the catalytic cleft, exhibited virtually complete abrogation of kinase function.
Phosphorylation of S710 is most likely not involved in the regulation of the subcellular distribution of STAT5A, since mutants designed to impair (STAT5AS710A) or to mimic (STAT5AS710D) serine phosphorylation could not rescue the SFK mediated block in nuclear accumulation of STAT5A.
In cultured cells, the Arg60Leu mutant was shown to impair phospholipase C PLCC) activation.
For example, expression of the catalytically dead C124S mutant was sufficient to impair glioma cell invasion [ 22] and PTEN can inhibit glioma cell migration through its C2 domain alone, in the absence of the catalytic domain [ 21].
It was recently proposed that the reduction observed in the reaction rate constant of a mutant enzyme – designed to impair the dynamics of this loop – was the consequence of the suppression of millisecond time-scale motions that allow the enzyme to sample activated reactant conformations [86].
