- In 1995, Visconti and colleagues included protein tyrosine phosphorylation (PTP) of proteins Mx 40,000-120,000 in the capacitation process.
- In exploring PTP, these researchers discovered the albumin, bicarbonate, and calcium requirements for PTP.
- In a following article, they were able to use cAMP analogs in place of albumin, bicarbonate, and calcium.
- After reviewing the previous aspects of our capacitation model, the requirement for bicarbonate can be translated to a requirement for cAMP and cAMP-dependent PKA signaling, earlier in capacitation.
- Visconti et al in 1995 showed that inhibition of PKA by H-89 inhibited PTP in a dose-dependent manner, up to 10uM. However, inhibiting protein kinase C had no effect on PTP, suggesting that this process relies on PKA instead.
- Hess and colleagues evidenced the requirement of sAC activation for PTP. When comparing null sAC sperm (mice with all sperm lacking sAC) to sperm from normal mice in capacitation media, the normal sperm exhibited characterized PTP patterns, which were not seen in null sAC sperm.
- Although PTP fits well within the current model of capacitation, the direct initiation of PTP remains unclear.
- Proposed models include:
- Stimulation of tyrosine kinase by PKA directly or indirectly (evidenced by findings of these tyrosine kinases in spermatozoa)
- Inhibition of phosphotyrosine phosphatase
- Phosphorylation of serine or threonine residues by PKA (possible because serine and threonine are phosphorylated before tyrosine)
- The actual tyrosine phosophoproteins in mice are testis-specific aldolases, voltage-dependent anion channel 2, glutathione-S-transferase, NADH dehydrogenase Fe-S protein 3, acrosin-binding protein precursor, proteasome subunit alpha, pyruvate dehydrogenase E1, tubulin beta 5, and cytochrome b-c1 complex subunit 1.
- Recent research suggests that these phosphoproteins may play a role for glycolysis during capacitation.