Lecture 4 - Protein Phosphatases

Question 1

Substrate Recognition by Protein Phosphatases:

Answer 1

Protein Phosphatases do not generally recognise consensus sequences around the target phosphorylated residue

Protein Phosphatases recognise other other molecular features of their substrates in addition to the phosphorylation site.

Question 2

Substrate Recognition by Protein Kinases:

Answer 2

Primary sequence of short motif flanking the residue to be phosphorylated determines specificity.

Note: Distal docking sites, scaffold proteins, and targeting to subcellular locations can also influence substrate selection.

Question 3

The depth of the catalytic pocket is one determinant of phosphoresidue specificity of Protein Phosphatases
TRUE

Answer 3

TRUE

Question 4

Protein Ser/Thr Phosphatases have SHALLOWER/DEEPER active sites than that of Tyr PPs:

Answer 4

Protein Ser/Thr Phosphatases have SHALLOWER active sites than that of Tyr PPs:

These shallower active sites do not accommodate phosphoTyrosine (as it is too long).

Question 5

Toxic Inhibitors of Ser/Thr Protein Phosphatases:

Answer 5

• Okadaic Acid
• Calyculin A
• Fostriecin
• Microcystin-LR
• Tautomycin
• Cantharidin

Question 6

Okadaic Acid and Microcystin are “tight-binding inhibitors” that DO/DO NOT follow standard Michaelis Menten Kinetics.

Answer 6

Okadaic Acid and Microcystin are “tight-binding inhibitors” that DO NOT follow standard Michaelis Menten Kinetics.

Question 7

Specificity of Ser/Thr Phosphatases is largely determined by association of BLANKS that affect subcellular localisation as well as substrate specificity

Answer 7

Specificity of Ser/Thr Phosphatases is largely determined by association of regulatory subunits that affect subcellular localisation as well as substrate specificity

Question 8

The regulatory subunit “MYPT1” turns the broad-specificity PP1C catalytic subunit into a myosin light chain (MLC)-specific phosphatase
TRUE OR FALSE

Answer 8

TRUE

Question 9

PP1:

Answer 9

Protein Phosphatase 1
A Protein Ser/Thr Phosphatase
PP1 regulates many processes in different cell types
PP1 is highly specific and highly regulated

Question 10

Targeting Subunits of PP1:

Answer 10

1. Targeting or localisation i.e. Bring phosphatase into vicinity of its substrates
2. Alter the substrate specificity of the PP1 catalytic subunit
3. Mediate regulation of PP1 activity

Question 11

The same catalytic subunit can be differentially controlled in different circumstances due to its selective regulation by a plethora of regulatory subunits
TRUE OR FALSE

Answer 11

TRUE